Editing Off-label use (section)

==Society and culture==
Drug manufacturers [[Marketing of off-label use|market drugs for off-label use]] in a range of ways. Marketing practices around off-label use have caused [[List of off-label promotion pharmaceutical settlements|various of lawsuits and settlements about inappropriately promoting drugs]]. Some of those lawsuits have ended granting the [[list of largest pharmaceutical settlements|largest pharmaceutical settlements]] in the world.

In the United States in 2017, the government is considering allowing [[direct-to-consumer advertising]] to promote off-label drug use.<ref>{{cite web |last1=Carr |first1=Teresa |title=FDA Considers Allowing Drug Ads for Unapproved Treatments |url=http://www.consumerreports.org/drugs/fda-considers-allowing-drug-ads-for-unapproved-treatments/ |website=Consumer Reports |access-date=3 April 2017 |date=9 November 2016}}</ref> The appointment of [[Scott Gottlieb]] to become head of the United States [[Food and Drug Administration]] (FDA) furthered discussion, as this person advocates to allow that sort of promotion.<ref>{{cite web |last1=Brill |first1=Steven |title=It's open season for off-label drug promotion |url=https://www.axios.com/its-open-season-for-off-label-drug-promotion-2209853447.html |website=Axios |access-date=24 March 2017 |language=en |date=24 January 2017}}</ref><ref>{{cite news |last1=McGinley |first1=Laurie |last2=Johnson |first2=Carolyn Y. |title=Trump to select Scott Gottlieb, a physician with deep drug-industry ties, to run the FDA |url=https://www.washingtonpost.com/news/to-your-health/wp/2017/03/10/trump-selects-scott-gottlieb-a-physician-with-deep-drug-industry-ties-to-run-the-fda |newspaper=Washington Post |access-date=24 March 2017 |date=10 March 2017}}</ref>

===Regulation in the United States===

In the United States, once a drug has been approved for sale for one purpose, physicians are free to [[medical prescription|prescribe]] it for any other purpose that in their professional judgment is both safe and effective, and are not limited to official, [[Food and Drug Administration|FDA]]-approved indications.<ref name=buckman /><ref>{{cite journal |last1=Beck |first1=James M. |last2=Azari |first2=Elizabeth D. |title=FDA, Off-Label Use, and Informed Consent: Debunking Myths and Misconceptions |journal=Food and Drug Law Journal |date=1998 |volume=53 |issue=1 |pages=76–80 |pmid=11795338 |url=https://www.druganddevicelawblog.com/wp-content/uploads/sites/30/2011/10/Beck-1998-FDLJ-Off-Label-Use-Article.pdf |access-date=21 September 2022}}</ref> [[Pharmaceutical]] [[list of pharmaceutical companies|companies]] are not allowed to promote a drug for any other purpose without formal FDA approval. Marketing information for the drug will list one or more indications, that is, [[illness]]es or medical conditions for which the drug has been shown to be both safe and effective.

This off-label prescribing is most commonly done with older, generic medications that have found new uses but have not had the formal (and often costly) applications and studies required by the FDA to formally approve the drug for these new indications. However, there is often extensive medical literature to support the off-label use.

A leading example of how [[regulatory agency|regulatory agencies]] approach off-label use is provided by the FDA's [[Center for Drug Evaluation and Research]], which reviews a company's [[New Drug Application]] (NDA) for [[clinical trials|clinical trial]] data to see if the results support the drug for a specific use or indication.<ref>{{cite web |url=https://www.fda.gov/Drugs/DevelopmentApprovalProcess/default.htm |archive-url=https://web.archive.org/web/20090603081757/http://www.fda.gov/Drugs/DevelopmentApprovalProcess/default.htm |url-status=dead |archive-date=June 3, 2009 |title=Development & Approval Process (Drugs) |publisher=Food and Drug Administration |date=2009-10-27 |access-date=2011-11-21}}</ref> If satisfied that the drug is safe and effective, the drug's manufacturer and the FDA agree on specific language describing dosage, route of administration, and other information to be included on the drug's label. More detail is included in the drug's package insert.

The FDA approves a drug for prescription use, and continues to regulate the [[pharmaceutical industry]]'s promotional practices for that drug through the work of the Office of Prescription Drug Promotion (OPDP, formerly the Division for Drug Marketing, Advertisement and Communication (DDMAC).<ref>{{cite web |url=https://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm |archive-url=https://web.archive.org/web/20090616104147/http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm |url-status=dead |archive-date=June 16, 2009 |title=The Office of Prescription Drug Promotion (OPDP) |publisher=Food and Drug Administration |date=2008-03-25 |access-date=2011-11-21}}</ref> The FDA does not have the legal authority to regulate the practice of the medicine, and the [[physician]] may prescribe a drug off-label.<ref name=buckman>{{cite court |litigants=Buckman Co. v. Plaintiffs' Legal Comm. |court=U.S.S.Ct. |vol=531 |reporter=U.S. |opinion=341 |date=2001 |url=https://www.law.cornell.edu/supct/html/98-1768.ZO.html |quote=the FDCA expressly states in part that '[n]othing in this chapter shall be construed to limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease within a legitimate health care practitioner-patient relationship.' 21 U.S.C. § 396 (1994 ed., Supp. IV).}}</ref> Contrary to popular notion, it is legal in the United States and in many other countries to use drugs off-label, including controlled substances such as opiates. [[Actiq]], for example, is commonly prescribed off-label even though it is a [[Schedule II controlled substance]]. While it would be legal for a physician to independently decide to prescribe a drug such as Actiq off-label, it is illegal for the company to promote off-label uses to prescribers. In fact, [[Cephalon]], the maker of Actiq, was fined for illegal promotion of the drug in September 2008.<ref>{{cite press release |url=http://www.usdoj.gov/archive/opa/pr/2008/September/08-civ-860.html |url-status=live |archive-url=https://wayback.archive-it.org/all/20150713095048/http://www.justice.gov/archive/opa/pr/2008/September/08-civ-860.html |archive-date=2015-07-13 |title=Biopharmaceutical Company, Cephalon, to Pay $425 Million & Enter Plea to Resolve Allegations of Off-Label Marketing |date=September 29, 2008 |publisher=[[United States Department of Justice]]}}</ref> Under the [[Federal Food, Drug, and Cosmetic Act|Food, Drug, and Cosmetic Act (FDCA)]] at U.S.C. 21 §§301-97, manufacturers are prohibited from directly marketing a drug for a use other than the FDA-approved indication. However, in December 2012, the [[United States Court of Appeals for the Second Circuit|United States Second Circuit Court]] found that promotion of off-label uses by a company sales representative was considered to be protected speech per the First Amendment.<ref>{{cite web |url=https://blogs.findlaw.com/second_circuit/2012/12/off-label-use-promotion-is-protected-free-speech.html |title=Off-Label Use Promotion is Protected Free Speech |website=Findlaw |date=2012-12-04 |access-date=2014-06-26}}</ref> In addition, the Food and Drug Administration Modernization Act of 1997 created an exception to the prohibition of off-label marketing, allowing manufacturers to provide medical practitioners with publications on off-label uses of a drug, in response to an unsolicited request.<ref>21 U.S.C. §360aaa-6</ref> In 2004, the federal government and whistleblower [[David Franklin (scientist)|David Franklin]] reached a $430 million settlement in ''[[Franklin v. Parke-Davis]]'' to resolve claims that [[Pfizer|Warner-Lambert]] engaged in off-label promotion of [[Gabapentin|Neurontin]] in violation of the FDCA and the [[False Claims Act]]. At the time, the settlement was [[List of largest pharmaceutical settlements in the United States|one of the largest]] recoveries against a pharmaceutical company in U.S. history, and the [[List of off-label promotion pharmaceutical settlements|first off-label promotion settlement]] in U.S. history.<ref>{{cite press release |url=https://www.justice.gov/opa/pr/2004/May/04_civ_322.htm |title=Warner-Lambert to Pay $430 Million to Resolve Criminal & Civil Health Care Liability Relating to Off-Label Promotion |publisher=[[United States Department of Justice]] |date=2004-05-13 |access-date=2013-04-30}}</ref>

Litigation around the marketing of [[ethyl eicosapentaenoic acid]] (E-EPA, branded as "Vascepa") by [[Amarin Corporation]] led to a 2015 court decision that has changed the FDA's approach to off-label marketing. E-EPA was the second [[fish oil]] drug to be approved, after [[omega-3-acid ethyl esters|omega−3-acid ethyl esters]] ([[GlaxoSmithKline]]'s Lovaza which was approved in 2004<ref name=PBM2005>VHA Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel (October 2005). [http://www.pbm.va.gov/clinicalguidance/drugmonographs/Omega3acidethylestersLovazaformerlyOmacor.pdf "National PBM Drug Monograph Omega-3-acid ethyl esters (Lovaza, formerly Omacor)"].</ref>) and sales were not as robust at Amarin had hoped. The labels for the two drugs were similar, but doctors prescribed Lovaza for people who had triglycerides lower than 500&nbsp;mg/dL based on some clinical evidence. Amarin wanted to actively market E-EPA for that population as well which would have greatly expanded its revenue, and applied to the FDA for permission to do so in 2013, which the FDA denied.<ref>{{cite news |first=Matthew |last=Herper |work=[[Forbes]] |date=17 October 2013 |url=https://www.forbes.com/sites/matthewherper/2013/10/17/why-the-fda-is-right-to-block-amarins-push-to-market-fish-oil-to-millions |title=Why The FDA Is Right To Block Amarin's Push To Market Fish Oil To Millions}}</ref>  In response, in May 2015 Amarin sued the FDA for infringing its [[First Amendment]] rights,<ref>{{cite news |first=Katie |last=Thomas |newspaper=The New York Times |date=7 May 2015 |url=https://www.nytimes.com/2015/05/08/business/drugmaker-sues-fda-over-right-to-discuss-off-label-uses.html |title=Drugmaker Sues F.D.A. Over Right to Discuss Off-Label Uses | access-date=17 May 2017}}</ref> and in August 2015 a judge ruled that the FDA could not "prohibit the truthful promotion of a drug for unapproved uses because doing so would violate the protection of free speech".<ref>{{cite news |first=Andrew |last=Pollack |work=[[The New York Times]] |date=7 August 2015 |url=https://www.nytimes.com/2015/08/08/business/court-forbids-fda-from-blocking-truthful-promotion-of-drug.html |title=Court Forbids F.D.A. From Blocking Truthful Promotion of Drug}}</ref> The ruling left open the question of what the FDA would allow Amarin to say about E-EPA, and in March 2016 the FDA and Amarin agreed that Amarin would submit specific marketing material to the FDA for the FDA to review, and if the parties disagreed on whether the material was truthful, they would seek a judge to mediate.<ref>{{cite news |first=Katie |last=Thomas |work=[[The New York Times]] |date=8 March 2016 |url=https://www.nytimes.com/2016/03/09/business/fda-deal-allows-amarin-to-promote-drug-for-off-label-use.html |title=F.D.A. Deal Allows Amarin to Promote Drug for Off-Label Use}}</ref>

===Regulation in the United Kingdom===
Physicians in the United Kingdom can prescribe medications off-label. According to [[General Medical Council]] guidance, the physician must be satisfied that there is sufficient evidence or experience of using the medicine to demonstrate safety and efficacy. Prescribing may be necessary when no suitably licensed medicine is available to meet the patient's need (or when the prescribing is part of approved research).<ref>{{cite web |author=General Medical Council |title=Good Practice in Prescribing and Managing Medicines and Devices |publisher=[[General Medical Council]] |type=published guidance |date=December 2014 |orig-year=first published February 2013 |pages=10–11 |url=https://www.gmc-uk.org/ethical-guidance/ethical-guidance-for-doctors/prescribing-and-managing-medicines-and-devices |access-date=24 May 2018 |format=PDF}}</ref>