Talk:Off-label use

Physician assisted suicide

I am not qualified to do so, but it would be appropriate to have a discussion in the article of the Oregon Death With Dignity act. The U.S. Attorney General attempted to block that state-enacted law by appealing to the illegality of off-label use of controlled substances for physician-assisted suicide. Diogenes 17:45, 30 September 2005 (UTC)

Amphetamine

Amphetamine is a scheduled substance, yet commonly prescribed off-label, as the article indeed says. At the same time, the article says that scheduled substances cannot be prescribed off-label. Why the discrepancy? Is there a legal distinction that causes it? — Preceding unsigned comment added by 194.109.198.99 (talk • contribs) 00:30, 26 June 2006 (UTC)

Off-label use is a murky matter, and whether any particular scheduled drug is treated as off-limits by the DEA is more a matter of practical enforcement than of any written law. On an unrelated note, a more international view would be nice-- how does this work in the UK, or in the EU for instance? Kajerm — Preceding unsigned comment added by Kajerm (talk • contribs) 17:28, 9 August 2006 (UTC)

Disputed

The article incorrectly states that Atomoxetine (Strattera) is the only drug with FDA approval in the U.S. for adult ADHD. Since August of 2004, Adderall XR, an extended release amphetamine, has also been approved for this use.[1][2]Hans Walling 18:25, 25 April 2007 (UTC)

There is an article stating that it is the *first* drug approved for adult ADHD [3], but as you mentioned it's not the only. It's the first (and currently may be only) non-stimulant. But I question the usefulness of this example of off-label use since there is a stimulant used on-label for adult ADHD, and I think the way the paragraph is written really doesn't get to the point. Perigrini (talk) 17:48, 4 October 2010 (UTC)

According to recent discussions (May 2007) with FDA officials, the practice of writing "off-label" prescriptions for narcoticsIS allowed by physicians without penalty. In the case discussed, the narcotic drug "Actiq", or generic fentanyl lollipops, are currently used for breakthrough pain in many diseases. And it is documented in other articles found on the internet and in magazines that only 1% of the prescriptions for this medication are written for the purpose marketed by the pharmaceutical company. Physicians have found a way of treating other diseases, besides cancer, whose sufferers can find no other medication unless their physician is willing to write "off-label" prescriptions to relieve the severe pain of their patients. Rebeccaj1009 00:34, 23 May 2007 (UTC)

It is perfectly legal in the U.S. to prescribe controlled substances off-label. It is, however, illegal to market drugs for off-label uses. Many controlled substances are written off-label. The most common is probably Actiq, which is only FDA-approved for "breakthrough cancer pain" but is prescribed for all sorts of moderate to severe non-cancer pain. It is worth noting that all the citations to the alleged "fact" that controlled substances are legally treated different than other FDA approved medications contains NO citation whatsoever. It is important that this false, and very unfortunate misconception not be propagated any further. I'm going to attempt to correct this entry again, and hopefully the erroneous information won't be put back by whomever it is who thinks they know what they're talking about but clearly does not. For what it's worth, I am a lawyer (though none of this is intended to be, or may be taken as, legal advice). —Preceding unsigned comment added by 98.196.110.71 (talk) 09:58, 22 March 2008 (UTC)

Drug and device

I think the article should indicate that it is drugs and devices that can be used off label. In the opening I would be inclined to say "Off-label use is the practice of prescribing drugs or medical devices for a purpose outside the scope of the product's approved label, most often concerning the drug's or the device's indication for use." Then throughout the article the language should reflect both drugs and devices. An example of using a device off label would be using a hemodialysis machine for home nocturnal dialysis www.homedialysis.org/files/pdf/resources/links/HomeHemoFDAMeeting.pdf BillpSea (talk) 18:20, 5 January 2008 (UTC)

Bevacizumab (Avastin)

The examples section says that clinical results for intravitreal injections of Avastin are anecdotal. There is a growing body of research being published in reputable medical journals worldwide indicating that it is a valid treatment. To date, calling the results anecdotal is an opinion, and thus not in keeping with WP:NPOV. That is why I have deleted the conjecture at the end of the example.Garvin ^Talk 02:41, 10 April 2009 (UTC)

Off-label prescribing for children

Am I correct in believing, and would it be useful to add to the article (given suitable citations), that many if not most of the drugs that physicians prescribe for children are being prescribed off-label, because ethical considerations make it very difficult to conduct drugs trials on child subjects, and consequently most drugs are not approved for them? 87.81.230.195 (talk) 15:08, 30 December 2009 (UTC)

Numerous flagrant violations of balance

This article incorrectly states the law on off label prescribing of off label drugs, it also is unbalanced, citing only positive examples of off-label use, and not the numerous examples of off-label ADR, such as fen-phen. It also does not talk about how drug companies have ghosted or otherwise planted research in an effort to make it seem as if a drug had had independent clinical research proving an off-label use, when in fact it had been drawn from the data already rejected by FDA, for example Merck and Vioxx. 71.174.43.137 (talk) 07:52, 30 January 2010 (UTC)

If you have reliable sources for this, why don't you add a criticism/controvery section? stmrlbs|talk 16:18, 30 January 2010 (UTC)

Transition to on-label use

Either this article or another article linked from here should discuss the process to get an off-label use approved on-label. For example, in the United States, the FDA approved Zyban (bupropion for smoking cessation) after Wellbutrin (bupropion for clinical depression), and Revatio (sildenafil citrate for heart therapy) was approved after Viagra (sildenafil citrate for erectile dysfunction). Is it just a New Drug Application that reuses the previous phase I, or is there a separate application for this? --Damian Yerrick (talk | stalk) 12:16, 22 August 2010 (UTC)

Globalise

This article deals with the matter entirely from the US point of view - starting from the lengthy "example" in the lede to the "Examples" section where "approved" relates to FDA approval, and "Schedule II drug" is irrelevant and not understandable for non-Americans. Thank you to improve. kashmiri ^TALK 10:02, 14 December 2014 (UTC)

Just moved large portions from the lede down to the United States section. Still, the globalisation issue remains. kashmiri ^TALK 10:23, 14 December 2014 (UTC)

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History of off-label use - origins in thalidomide?

One story about the origins of off-label use is that the concept originated around thalidomide. When that drug caused problems, then various consumer rights advocates blamed off-label use as the practice at the origin of the problem. There are sources cited in thalidomide and Kefauver Harris Amendment which suggest that distinguishing approved and off-label use became an issue around 1962. This might say more.

• Peltzman, Sam (1 January 1973). "An Evaluation of Consumer Protection Legislation: The 1962 Drug Amendments". Journal of Political Economy. 81 (5): 1049–1091.
• Fintel, Bara; Samaras, Athena T.; Carias, Edson (28 July 2009). "The Thalidomide Tragedy: Lessons for Drug Safety and Regulation". helix.northwestern.edu.

There currently is no history section in the article. There should be. I am not sure right now where to begin except by gathering sources. Blue Rasberry (talk) 17:01, 24 March 2017 (UTC)

There seem to be multiple laws regarding off-label use in various countries, all with origins in thalidomide.

• Kefauver Harris Amendment
• Medicines Act 1968
• Directive 65/65/EEC

I wonder if there are other laws in other countries with origins from this incident, around this time. Here is a partial narrative of the time.

• Rägo, Lembit; Santoso, Budiono. "Drug Regulation: History, Present and Future" (PDF). World Health Organization. Retrieved 24 March 2017.

There seem to be lots of publications telling versions of this story. I do not know which source is a comprehensive origin story. Lots of sources that I see gloss over the history, presuming that the reader is already familiar with it and need orientation. At a glance, it seems like 50+ publications tell a ~1 page summary of the story. There could be an entire book about this somewhere or at least multiple papers giving a deep perspective of some aspect of this. Blue Rasberry (talk) 17:57, 24 March 2017 (UTC)

Big money big lawsuits - how to describe here

There is a narrative which ought to be in this article but currently is not. Consider

• List of off-label promotion pharmaceutical settlements
• list of largest pharmaceutical settlements

In Wikipedia's documentation of the biggest pharma lawsuits, off-label use stands out as the recurring major problem. It seems like if there is a massive medical tragedy which goes to court and gets settled, then by these lists, off-label use is the legal conflict. There are about USD 10 billion dollars in lawsuits here and I expect that every one of those lawsuits involves however many people and stories 100s of millions of dollars can influence. Right now, Wikipedia does not have good coverage of individual lawsuits, but I expect that any 100+ million dollar lawsuit would be notable to have its own Wikipedia article. Also, this article does not really describe how frequent it is for off-label use to lead to the biggest legal settlements that happen in any context.

I am not sure where to begin describing this but somehow, this article and those "list of settlement" articles should be better connected to each other because there is so much overlap in scope. Blue Rasberry (talk) 17:09, 24 March 2017 (UTC)

Off-label use policy change in United States

Various sources are reporting that Scott Gottlieb is likely to become the head of the Food and Drug Administration and that one of the policy changes he will institute will be changes to permit more advertising of off-label use of drugs in the United States.

• Brill, Steven (24 January 2017). "It's open season for off-label drug promotion". Axios. Retrieved 24 March 2017.
• McGinley, Laurie; Johnson, Carolyn Y. (10 March 2017). "Trump to select Scott Gottlieb, a physician with deep drug-industry ties, to run the FDA". Washington Post. Retrieved 24 March 2017.
• Mixter, Bronwyn (14 March 2017). "Trump's FDA Nominee Spurs Concerns About Drug Approvals, Off-Label Promotion". www.bna.com.
• Neel, Joe (10 March 2017). "Trump Chooses Dr. Scott Gottlieb To Head Food And Drug Administration". NPR.org. Retrieved 24 March 2017.

I am not sure how this information should go into the article. From one perspective, this article should not focus on the laws of one country. From another perspective, the United States has significant influence on global access to medicine. Other countries recognize the precedent of United States law, companies based in the US fund the most pharma research, the US is the world's single largest drug market, and the US produces more medicine related media than any other country. There is currently a tag on this article which says it is too slanted to the United States perspective, and I think this is a valid concern. I am not sure what to do. Perhaps some information should be cut, and other information put in, and perhaps there should be an individual article on "Off-label use in the United States" but I do not think there is enough content here to do a clean fork into a US-only article without more research and writing.

I am not sure what to do next. Blue Rasberry (talk) 17:48, 24 March 2017 (UTC)

Moved research section here from article

The research section which was in the article described some smaller but nationally representative survey results from 2009 in the United States. This article already has problems being too directed at the United States and not written for a global audience. That combined with the information being survey results made me think it would be better to remove the research section, even if I have no other text with with to replace it. Also, the research section was being used as a holding area for a list of academic papers which have been listed over time since before. Wikipedia prefers summarized text in articles and is never supposed to have bibliographies of this sort in the body of the article. I am cleaning this!

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Research relating to off-label use

According to a national random mail survey of 599 primary care physicians and 600 psychiatrists in the United States, there is a strong indication between a physician’s belief that a use is approved and the known evidence supporting that use, although almost half of physicians believed one off-label use that had little or no supporting evidence. This shows that there is a need for informing physicians about the evidence supporting off-label prescriptions, although the FDA only regulates drug marketing not drug prescribing.

• Alexander GC. Clinical prescribing (and off-label use) in a second-best world. Medical care. 2010;48:285-287. (Invited editorial)
• Tabarrok A (2000). "Assessing the FDA via the anomaly of off-label drug prescribing". Independent Review. 1: 25–53.
• Walton SM, Schumock GT, Lee KV, Alexander GC, Melzter DO, Stafford RS (2008). "Prioritizing medications for policy and research initiatives examining off-label prescribing". Pharmocotherapy. 28: 1443–1452.
• Harold J. DeMonaco; Ayfer Ali; Eric Von Hippel (2006). "The Major Role of Clinicians in the Discovery of Off-Label Drug Therapies" (PDF). Pharmacotherapy. 26 (3): 323–332. doi:10.1592/phco.26.3.323.
• Chen DT, Wynia MK, Moloney RM, Alexander GC (2009). "Physician knowledge of the FDA-approved indications of commonly prescribed drugs: results of a national survey". Pharmacoepidemiology and Drug Safety. 18 (11): 1–7. doi:10.1002/pds.1825. PMID 19697444.

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Blue Rasberry (talk) 14:40, 3 April 2017 (UTC)

Forked content into new article - Marketing of off-label use

See Marketing of off-label use.

I established that article with the content which was in the "controversies" section here. Controversies was never a good name for that section, but it is common in Wikipedia to put lawsuits in a controversy section. That section actually had a discussion about drug advertising, so I cut and pasted it all to there. The content which I moved was at Off-label use#Controversies from the April 2017 version of this article.

I discuss more on the talk page there at Talk:Marketing of off-label use. Blue Rasberry (talk) 15:40, 3 April 2017 (UTC)

Off-licensed drug

There is an article called Off-licensed drug which is sort of like this one, but which I think is a misunderstanding of the concept. No sources are cited and it is a mess, so I just nominated it for deletion at Wikipedia:Articles for deletion/Off-licensed drug.

It was linked from this article in a "see also" section, so because of that and the similarity I am raising the issue here. Blue Rasberry (talk) 15:50, 3 April 2017 (UTC)

New article - List of drugs known for off-label use

I just established List of drugs known for off-label use as its own article. See Talk:List of drugs known for off-label use for an explanation. In summary, this list was becoming indiscriminate and could grow indefinitely. Maybe it should not be a Wikipedia article at all, but also, I think it does not belong here either. Blue Rasberry (talk) 16:10, 3 April 2017 (UTC)

Review of available sources

I found the full texts of all of these available to read online.

In considering what sources ought to be cited in this article, one challenge to address is when to use sources talking about the United States. This source gives a history of the laws and regulations around off-label use in the United States.

• O'Reilly, J; Dalal, A (2003). "Off-label or out of bounds? Prescriber and marketer liability for unapproved uses of FDA-approved drugs" (PDF). Annals of health law. 12 (2): 295–324. PMID 12856461.

Another article starts by citing that article: "Americans have historically had perhaps the world’s most rigorous regulatory system for the protection of medical product consumers."

• Ventola, CL (August 2009). "Off-label drug information: regulation, distribution, evaluation, and related controversies". P & T : a peer-reviewed journal for formulary management. 34 (8): 428–40. PMID 20140107.

I think both of these articles are fair sources to use for summarizing in Wikipedia some of the broad discussions for and against off-label use. Many of the available sources are United States-centric.

Here are some more sources which I examined -

• "Shopper's Guide to Prescription Drugs - "Off label" Drug Use" (PDF). Consumer Reports. 2007. Retrieved 3 April 2017.

This source lists how patients and physicians use general classes of drugs for off-label purposes. Also, there is an explanation of why off-label use is common in cancer treatment and children's off-label use of drugs approved only for adults.

• Mithani, Z (1 July 2012). "Informed consent for off-label use of prescription medications". AMA Journal of Ethics. 14 (7): 576–81. PMID 23351297.

This gives pros and cons about whether a physician should tell their patient whether the drug is off-label. This includes some surprising arguments that off-label use is preferable and that patient ignorance might be best.

• Lenk, Christian; Duttge, Gunnar (July 2014). "Ethical and legal framework and regulation for off-label use: European perspective". Therapeutics and Clinical Risk Management: 537. doi:10.2147/TCRM.S40232.{{cite journal}}: CS1 maint: unflagged free DOI (link)

Non-American context, much needed

• Thompson III, Fred (31 March 2016). "How U.S. regulation prevented off-label use of a drug and a subsequent birth defect disaster". www.motleyrice.com. Retrieved 3 April 2017.

Normally I would never cite a source like this. This is a company blog for a law firm. However, this is a fair telling of a story in a short way. The thalidomide narrative needs to be summarized here with an emphasis on the "off-label" aspect of that and a law firm would write it that way. Surely there is more traditional source to cite than this one but it is interesting.

• Sirven, Joseph I. (June 2010). "New Uses for Older Drugs: The Tales of Aspirin, Thalidomide, and Gabapentin". Mayo Clinic ::Proceedings. 85 (6): 508–511. doi:10.4065/mcp.2010.0267.

If the wiki article needs iconic examples of off-label use then this article presents some stories as cultural history of medicine.

• Mello, MM; Studdert, DM; Brennan, TA (9 April 2009). "Shifting terrain in the regulation of off-label promotion of pharmaceuticals". The New England journal of medicine. 360 (15): 1557–66. PMID 19357413.

"Journal reprints are among the most visible forms of promotion" - The article currently lack a description of just how off-label use comes to happen and this sort of information is key.

• Gazarian, M; Kelly, M; McPhee, JR; Graudins, LV; Ward, RL; Campbell, TJ (20 November 2006). "Off-label use of medicines: consensus recommendations for evaluating appropriateness". The Medical journal of Australia. 185 (10): 544–8. PMID 17115966.

Exceptionally well-written basic definition of the concept, plus this was written by Australians who are drawing from literature in the US and UK. This is a great perspective in itself, and additionally valuable for being a non-US/UK voice.

• Lindell-Osuagwu, L.; Korhonen, M. J.; Saano, S.; Helin-Tanninen, M.; Naaranlahti, T.; Kokki, H. (June 2009). "Off-label and unlicensed drug prescribing in three paediatric wards in Finland and review of the international literature". Journal of Clinical Pharmacy and Therapeutics. 34 (3): 277–287. doi:10.1111/j.1365-2710.2008.01005.x.

This is great for being an international review of practice, and for talking about children, and for being non-US/UK.

Blue Rasberry (talk) 22:53, 3 April 2017 (UTC)

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Frequency of off-label use

Line 21 (U.S. General Accounting Office) should be (The U.S. Government Accountability Office (GAO)), instead.

ThomasYehYeh (talk) 11:56, 12 November 2020 (UTC)