No Need for more regulation: Payors and their role in balancing the cost and safety considerations of off-label prescriptions

American Journal of Law and Medicine

Volumn 37, Issue 2-3, 2011, Pages 422-443

  Todd, Amy E ^a  

^a BOSTON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; FOOD AND DRUG ADMINISTRATION; GOVERNMENT REGULATION; HEALTH INSURANCE; HUMAN; LEGAL ASPECT; OFF LABEL DRUG USE; PRODUCT SAFETY; UNITED STATES;

CONSUMER PRODUCT SAFETY; GOVERNMENT REGULATION; HUMANS; INSURANCE, HEALTH; OFF-LABEL USE; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 80051835883     PISSN: 00988588     EISSN: None     Source Type: Journal    
DOI: 10.1177/009885881103700209     Document Type: Article

References (66)

1. Anne Martin et al., Recession Contributes to Slowest Annual Rate of Increase in Health Spending in Five Decades, 30 Health Aff. 11, 11 (2011).
2. The Henry J. Kaiser Family Foundation, U.S. Health Care Costs, http://www.kaiseredu.org/Issue-Modules/US-Health-Care-Costs/Background-Brief. aspx (last updated Mar., 2011).
3. Rebecca Dresser & Joel Frader, Off-Label Prescribing: A Call for Heightened Professional and Government Oversight, 37 J.L. Med. & Ethics 476, 477 (2009).
4. See Joshua Cohen et al., Off-Label Use Reimbursement, 64 Food & Drug L.J. 391, 396 (2009) (outlining the insurance industry's process for reimbursing drug claims).
5. Food, Drug, and Cosmetic Act, 21 U.S.C. §§ 301-399 (2006).
6. 8 Id. § 32l(p)(l). The FDA drug approval process has received much criticism for its lengthiness. Before a drug maker can submit an Investigational New Drug Application (IND), it must conduct investigations of the drug's effect on animals to determine if it is safe for human clinical trials. This may take as long as three and a half years. After approval of the IND, the drug must undergo three phases of clinical trials. Phase I trials test toxicity of the drug on humans to determine if it is safe, and takes six to twelve months to complete. Phase II trials test the therapeutic effectiveness on humans suffering from the condition, and takes eighteen months to two years to complete. Phase III consists of clinical trials to further develop effectiveness data, and can last for an average of three years. After completion of the three phases, the drug maker can submit a New Drug Application (NDA) to the FDA, which the agency approves within 180 days. Benjamin R. Rossen, FDA's Proposed Regulations to Expand Access to Investigational Drugs for Treatment Use: The Status Quo in the Guise of Reform, 64 Food & Drug L.J. 183, 187-88 (2009).
7. Carol R. Berry, The Dividing Line Between the Role of the FDA and the Practice of Medicine: A Historical and Current Analysis 2-10 (Jan. 1997) (unpublished paper, Harvard Law School) (on file with Legal Education Document Archive (LEDA), Harvard Law School).
8. Kaspar J. Stoffelmayr, Products Liability and "Off-Label" Uses of Prescriptions Drugs, 63 U. Chi. L. Rev. 275, 277 (1996).
9. In other words, a physician fails to act as would a similar physician in similar circumstances.
10. "[W]e find that a prescription drug's labeling or its PDR reference, when introduced along with other expert evidence on the standard of care, is admissible to assist the trier-of-fact to determine whether the drug presented an unacceptable risk to the patient." Richardson v. Miller, 44 S.W.3d 1, 17 (Tenn. Ct. App. 2000).
11. James B. Riley, Jr. & P. Aaron Basilius, Physicians' Liability for Off-Label Prescriptions, 6 Hematology & Oncology News & Issues 24, 26 (2007).
12. Id. There has been much commentary about the issue of informed consent in off-label prescribing.
13. See, e.g., Richard C. Ausness, "There's Danger Here, Cheriel": Liability for the Promotion and Marketing of Drugs and Medical Devices for Off-Label Uses, 73 Brook. L. Rev. 1253 (2008).
14. Margaret Z. Johns, Informed Consent: Requiring Doctors to Disclose Off-Label Prescriptions and Conflicts of Interest, 58 Hastings L.J. 967 (2007).
15. David C. Radley et al., Off-Label Prescribing Among Office-Based Physicians, 166 Archives Internal Med. 1021, 1023 (2006).
16. James M. Beck & Elizabeth D. Azari, FDA, Off-Label Use, and Informed Consent: Debunking Myths and Misconceptions, 53 Food & Drug L.J. 71, 80 (1998).
17. Mark Herrmann & Pearson Bownas, Keeping the Label Out of the Case, 103 Nw. U. L. Rev. 477, 478 (2009).
18. Mary Anne Pazanowski, FDA, Legal Experts Discuss Obstacles Facing Pediatric Product Development, 3 BNA Med. Devices L. & Industry Rep. 380 (May 20, 2009).
19. U.S. Food & Drug Ass'n, 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 3 (Jan. 2009), available at http://www.fda.gov/OHRMS/ DOCKETS/98fr/FDA-2008-D-0053-gdl.pdf (explaining that off-label uses or treatment regimens "may be important and may even constitute a medically recognized standard of care").
20. Veronica Henry, Off-Label Prescribing Legal Implications, 20 J. Legal Med. 365, 382 (1999).
21. Jeff Minerd, Most Off-Label Drug Use on Iffy Scientific Ground, MedPage Today (May 9, 2006), http://www.medpagetoday.com/PublicHealthPolicy/ HealthPolicy/3252.
22. Rick Nauert, Off-Label Use May Be Off-Track, Psych Central (Aug. 24, 2009), http://psychcentral.com/news/2009/08/24/off-label-use-may-be-off-track/ 7926.html.
23. Off-Label Drug Uses Wasting Millions, Raising Health Risks, The Medical News (Mar. 4, 2009, 10:14 PM), http://www.news-medical.net/news/2009/03/04/ 46510.aspx.
24. See also Will Meek, Off-Label Antipsychotic Use, Psych Central (Jan. 21, 2007), http://psychcentral.com/blog/archives/2007/0l/2l/off-label-antipsychotic- use/.
25. Steven R. Salbu, Off-Label Use, Prescription, and Marketing of FDA-Approved Drugs: An Assessment of Legislative and Regulatory Policy, 51 Fla. L. Rev. 181, 203 (1999).
26. "Any person who . . . knowingly presents, or causes to be presented, a false or fraudulent claim for payment or approval ... is liable to the United States Government for a civil penalty." False Claims Act, 31 U.S.C. § 3729(a)(1) (2006).
27. Thomas S. Crane, The Next Enforcement Wave-Off-Label Marketing of Medical Devices, 21 Health Law. 22, 22 (2009).
28. Randall S. Stafford, Regulating Off-Label Drug Use-Rethinking the Role of the FDA, 358 New Eng. J. Med. 1427, 1428 (2008).
29. Allergan also sued the Department of Justice, which has been involved in the prosecution of off-label drug promotion. Natasha Singer, Botox Maker's Suit Cites Free Speech, N.Y. Times, Oct. 3, 2009, at B3.
30. In September 2010, Allergan reached a settlement with the Department of Justice to resolve the criminal and civil claims against the company. Allergan pleaded guilty to a misdemeanor misbranding charge and agreed to pay $600 million. Allergan also agreed to drop its free speech claims. See Jon Kamp & Brent Kendall, Botox Allegations Settled with U.S. for $600 Million, Wall St. J. (Sept. 2, 2010), http://online.wsj.com/article/ SB10001424052748703882304575465371767239834.html.
31. The U.S. Supreme Court recently granted certiorari in Sorrel v. IMS Health Inc. to decide whether a Vermont law prohibiting pharmaceutical companies from using prescriber-identifiable data for marketing purposes restricts free trade in truthful information. Robert Barnes, Supreme Court to Hear Drug Data-Mining Case, Wash. Post (Jan. 7, 2011, 10:26 PM), http://www. washingtonpost.com/wp-dyn/content/article/2011/01/07/AR2011010705726.html. Although Sorrel differs in that it involves the treatment of personal patient data, a holding that such restrictions violate the First Amendment increase the likelihood that an Allergan-like constitutional challenge to the off-label marketing ban would be successful.
32. U.S. Gov't Accountability Office, FDA Faces Challenges Meeting Its Growing Medical Product Responsibilities and Should Develop Complete Estimates of Its Resource Needs 34-35 (2009) (finding that the FDA "cannot do all that is asked of it").
33. For a more thorough investigation of the Ketek incident, see David B. Ross, The FDA and the Case of Ketek, 356 New Eng. J. Med. 1601 (2007).
34. Brief for David B. Ross, & Stefan P. Kruszewski, as Amici Curiae Supporting Respondent, Wyeth v. Levine, 129 S. Ct. 1187 (2009) (No. 06-1249), 2008 WL 4642106 at *8-15.
35. Wyeth v. Levine, 129 S. Ct. 1187, 1202.
36. See John N. Joseph et al., Enforcement Related to Off- Label Marketing and Use of Drugs and Devices: Where Have We Been and Where Are We Going?, 1 J. Health & Life Sci. L. 73, 81 (2009) (noting that private insurers have denied reimbursement for off-label use of drugs).
37. See Barry R. Furrow et al., Health Law: Cases, Materials and Problems 122-25 (6th ed. 2008) (discussing state and federal authority to regulate the practice of medicine).
38. Maxwell J. Mehlman, Off-Label Prescribing, The Doctor Will See You Now (May 2005), http://www.thedoctorwillseeyounow.com/content/bioethics/artl971. html/.
39. Under Illinois law, an HMO that provides coverage for FDA approved drugs approved for the treatment of certain types of cancer shall not "exclude coverage of any drug on the basis that the drug has been prescribed for the treatment of a type of cancer for which the drug has not been approved by the federal Food and Drug Administration." 215 ILL. Comp. Stat. Ann. 125/4-6.3 (West 2009).
40. Alexander T. Tabarrok, Assessing the FDA via the Anomaly of Off-Label Drug Prescribing, 5 Indep. Rev. 25, 35-36 (2000).
41. Doctors Cannot Prescribe Abortion Pill for Off-Label Uses, Ohio Supreme Court Says, 18 BNA Health L. Rep. 920 (July 9, 2009) (discussing the result in Cordray v. Planned Parenthood Cincinnati Region, 911 N.E.2d 871 (Ohio 2009)).
42. Employee Retirement Income Security Act of 1974 (ERISA), Pub. L. No. 93-406, 88 Stat. 829 (codified as amended in scattered sections of 5 U.S.C., 18 U.S.C., 26 U.S.C., 29 U.S.C., and 42 U.S.C.).
43. See Leslie Pickering Francis, Legitimate Expectations, Unreasonable Beliefs, and Legally Mandated Coverage of Experimental Therapy, 1 Ind. Health L. Rev. 213, 234 (2004) (discussing the relationship between ERISA and off-label prescribing).
44. Mitchell Oates, Facilitating Informed Medical Treatment Through Production and Disclosure of Research Into Off-Label Uses of Pharmaceuticals, 80 N.Y.U. L. Rev. 1272, 1284-85 (2005). There are benefits of SNDA approval to the drug manufacturer, however, including the ability to freely market the off-label use. Id.
45. Joshua Cohen & Andrew Wilson, New Challenges to Medicare Fighting Beneficiary Access to mAbs, 1 mAbs 56, 56 (2009).
46. Richard A. Epstein, Against Permititis: Why Voluntary Organizations Should Regulate the Use of Cancer Drugs, 94 Minn. L. Rev. 1, 4-5 (2009).
47. Reed Abelson & Andrew Pollack, Medicare Widens Drugs It Accepts for Cancer, N.Y. Times, Jan. 27, 2009, at Al (noting that in some cases the reference guides motivating coverage determinations are linked to drug makers).
48. Press Release, Tufts Center for the Study of Drug Development, Three-Quarters of U.S. Health Plans Reimburse for Off-Label Uses of Prescription Drugs (Mar. 10, 2009), available at http://csdd.tufts.edu/files/uploads/mar- apr-pr.pdf (noting that most third-party payors rely on pharmaceutical compedia and/or peer-reviewed literature to inform reimbursement decisions).
49. See Roxanne Nelson, Compendia Guiding Off-Label Use of Cancer Drugs Inadequate, Medscape Medical News (Feb. 21, 2009), http://www.medscape.com/ viewarticle/588552(discussing Abernathy's study and noting inconsistency across compendia).
50. Agency for Healthcare Research & Quality, Dep't of Health and Human Servs., Compendia for Coverage of Off-Label Uses of Drugs and Biologics in an Anticancer Chemotherapeutic Regimen 3 (2007).
51. Tom Goss, Off-Label Use of Anticancer Therapies: Physician Prescribing Trends and the Impact of Payer Coverage Policy 3 (2005), available at http://accc-cancer.org/advocacy/pdf/PhRMAstudy.pdf (commissioned by the Association of Community Cancer Centers, the Biotechnology Industry Organization, and the Pharmaceutical Research and Manufacturers of America).
52. American Society of Clinical Oncology, Reimbursement for Cancer Treatment: Coverage of Off-Label Drug Indications, 24 J. Clinical Oncology 3206, 3206-07 (2006).
53. See Medicare: Senator Praises CMS Coding Decision On Reimbursement for Off-Label Avastin, 7 BNA Pharm. L. & Industry Rep. 1287 (Nov. 11, 2009) (describing a CMS coding change permitting physicians to prescribe cancer drugs for off-label uses).
54. S.C. Code Ann. § 38-71-275 (1976).
55. For example, in Ohio, no policy "shall limit or exclude coverage on the basis that the drug has not been approved by the United States food and drug administration for the treatment of a particular indication for which the drug has been prescribed . . . Ohio Rev. Code Ann. § 1751.66 (West 2010).
56. AHCA also limited the off-label uses of Neurontin's corresponding generic, gabapentin. Drew Douglas, State to Appeal Ruling That It Must Pay for Off-Label Uses of Epilepsy Medication, 15 BNA Health L. Rep. 306 (Mar. 16, 2006).
57. Quaresma v. BC Life & Health Ins. Co., 623 F. Supp. 2d 1110, 1135 (2007) (limiting Cal. Health & Safety Code § 1367-21 (West 2010) and Cal. Ins. Code § 10123.195 (West 2010) because they encroach on a relationship regulated by ERISA).
58. See Harold C. Sox, Editorial, Evaluating Off-Label Uses of Anticancer Drugs: Time for a Change, 150 Annals of Internal Med. 353, 354 (2009) (arguing that the approach where Medicare pays for off-label use of a drug if it is included in a compendia is too low a hurdle and is necessarily inconsistent).
59. Wyeth, 129 S. Ct. at 1202.
60. Henninger S. Bullock et al., Fifth Circuit, Joining Eighth Circuit, Holds Consumers "Failure to Warn" Claims Against Generic-Drug Makers Not Preempted by Federal Law (Jan. 25, 2010), http://www.mayerbrown.com/ publications/article.asp?id=8473&nid=6. In Demahy v. Actavis, the plaintiff alleged that the drug Reglan, manufactured by Actavis, which she used to treat gastric conditions, created a neurological condition.
61. CMS to Cover Warfarin Response Testing Only if Beneficiary in Specific Clinical Trial, 7 BNA Pharm. L. & Industry Rep. 948 (Aug. 14, 2009) for another example of a clinical trial requirement for coverage.
62. Nathaniel Weixel, Delivery System Reform Makes Treatments More Affordable, J&J Executive Says, 8 BNA Pharm. L. & Industry Rep. 255 (Feb. 19, 2010).
63. The NCD was originally prompted by safety and spending concerns along with "aggressive marketing practices." Id. at 403 (citing Stephanie Saul, Medicare Balks at Covering Johnson Heart Drug in Some Cases, N.Y. Times (Dec. 3, 2005), http://www.nytimes.eom/2005/l2/03/business/03drug.html?-r= 2&ref=stephaniesaul]).
64. Best Pharmaceuticals for Children Act (BPCA) of 2002, Pub. L. No. 107-109, 115 Stat. 1408 (2002) (codified as amended in scattered sections of 21 U.S.C. and 42 U.S.C.).
65. Patient Protection and Affordable Care Act of 2010, Pub. L. No. 111-148, 124 Stat. 119 § 6301 (2010).
66. See also Alex Nussbaum et al., Obamacare's Cost Scalpel, BusinessWeek (Mar. 24, 2010, 11:05 PM), http://www.businessweek.com/magazine/content/l0-14/ b4172064340424.htm (describing the comparative effectiveness research provisions).