Editing Off-label use (section)

==Frequency of off-label use==

Off-label use is very common. Generic drugs generally have no sponsor as their indications and use expands, and incentives are limited to initiate new clinical trials to generate additional data for approval agencies to expand indications of proprietary drugs.<ref name=nejm/> Up to one-fifth of all drugs are prescribed off-label and amongst psychiatric drugs, off-label use rises to 31%.<ref name = radley>{{cite journal |author1=David C. Radley |author2=Stan N. Finkelstein |author3=Randall S. Stafford |journal=[[Archives of Internal Medicine]] |year=2006 |volume=166 |issue=9 |pages=1021–1026 |title=Off-label Prescribing Among Office-Based Physicians |doi=10.1001/archinte.166.9.1021 |pmid=16682577| doi-access = }}</ref>

Among use of [[antipsychotic]] medications in the United States, a shift occurred from typical agents in 1995 (84% of all antipsychotic visits) to atypical agents by 2008 (93%). Atypical use has grown far beyond substitution for the now infrequently used typical agents.<ref name = alexander>{{cite journal |author1=Alexander GC |author2=Gallagher SA |author3=Mascola A |journal=[[Pharmacoepidemiology and Drug Safety]] |year=2011 |volume=20 |issue=2 |pages=177–184 |title=Increasing off-label use of antipsychotic medications |doi=10.1002/pds.2082 |pmid=21254289 |pmc=3069498}}</ref>

A 2009 study found that 62% of U.S. pediatric office visits from 2001 to 2004 included off-label prescribing, with younger children having a higher chance of receiving off-label prescriptions. Specialist physicians also prescribed off-label more frequently than general pediatricians.<ref>{{cite journal |first11=Alicia |last1=Bazzano |first2=Rita |last2=Mangione-Smith |first3=Matthias |last3=Schonlau |author3-link= Matthias Schonlau |first4=Marika |last4=Suttorp |first5=Robert H. |last5=Brook |title=Off-label prescribing to children in the United States outpatient setting. |journal=[[Ambulatory Pediatrics]] |year=2009 |volume=9 |pages=81–8 |doi=10.1016/j.acap.2008.11.010 |pmid=19329098 |issue=2}}</ref> In 2003, passage of the Pediatric Research Equity Act gave the FDA power to require pharmaceutical companies to perform clinical trials in all age groups in which clinical use is reasonably foreseeable. By some estimates, the number of clinical trials performed in children from 2002 to 2012 exceeded that in the prior 50 years.<ref>{{cite journal |vauthors=Christensen ML |title=Best pharmaceuticals for children act and pediatric research equity act: time for permanent status |journal=Journal of Pediatric Pharmacology and Therapeutics |volume=17 |issue=2 |pages=140–41 |year=2012 |pmid=23185144 |pmc=3470432 |doi=10.5863/1551-6776-17.2.140}}</ref>

In 2014, the American Academy of Pediatrics released a statement regarding off-label use of pharmaceuticals in children. The article recommends to pediatricians that "Off-label use is neither incorrect nor investigational if based on sound scientific evidence, expert medical judgment, or published literature" and that "Evidence, not label indication, remains the gold standard from which practitioners should draw when making therapeutic decisions for their patients." The statement further advocates additional support and additional incentives for clinical testing of drugs in children, and publication of all results irrespective of positive outcome.<ref>{{cite journal |vauthors=Frattarelli DA, Galinkin JL, Green TP, Johnson TD, Neville KA, Paul IM, Van Den Anker JN |title=Off-label use of drugs in children |journal=Pediatrics |volume=133 |issue=3 |pages=563–567 |year=2014 |pmid=24567009 |doi=10.1542/peds.2013-4060 |doi-access=free}}</ref>

A study published in 2006 found that off-label use was the most common in [[anticonvulsant]]s. The study also found that 73% of off-label use had little or no scientific support.<ref name=radley/>

By default, use of non-approved drugs is common in [[obstetrics]]. By 2010, during almost five decades of activity, the [[Food and Drug Administration]] (FDA) had approved only two drugs for obstetrical indications, namely [[Oxytocin (medication)|oxytocin]] and [[dinoprostone]].<ref name=wing>{{cite journal |vauthors=Wing DA, Powers B, Hickok D |title=U.S. Food and Drug Administration Drug Approval: Slow Advances in Obstetric Care in the United States |journal=[[Obstetrics & Gynecology (journal)|Obstetrics & Gynecology]] |doi=10.1097/AOG.0b013e3181d53843 |volume=115 |issue=4 |pages=825–33 |date=April 2010 |pmid=20308845}}</ref> A small market and the high risk of medicolegal action, as exemplified by the [[Bendectin]] case, may explain the reluctance to develop drugs for approval.<ref name=wing/>

Some drugs are used more frequently off-label than for their original, approved indications. A 1991 study by the U.S. [[Government Accountability Office|General Accounting Office]] found that one-third of all drug administrations to [[cancer]] patients were off-label, and more than half of cancer patients received at least one drug for an off-label indication. A 1997 survey of 200 cancer physicians by the [[American Enterprise Institute]] and the [[American Cancer Society]] found that 60% of them prescribed drugs off-label.<ref name="npr.org">{{cite web |work=Day to Day |url=https://www.npr.org/templates/story/story.php?storyId=95985619 |title=Prozac Isn't The Same In A Kid's Body |publisher=NPR |date=2008-10-22 |access-date=2011-11-21}}</ref><ref name="cancer01">{{cite web |url=http://www.cancer.gov/clinicaltrials/learning/approval-process-for-cancer-drugs/allpages#Anchor-Wh-36735 |title=Why is off-label use of drugs so common in cancer treatment? |publisher=National Cancer Institute |access-date=2009-07-12}}</ref> In some cases, patients may perceive the efficacy of treatments for off-label purposes to be higher than for their indicated purpose.<ref>{{cite journal |first1=Jeana |last1=Frost |first2=Sally |last2=Okun |first3=Timothy |last3=Vaughan |first4=James |last4=Heywood |first5=Paul |last5=Wicks |title=Patient-reported Outcomes as a Source of Evidence in Off-Label Prescribing: Analysis of Data From PatientsLikeMe |journal=[[Journal of Medical Internet Research]] |year=2011 |volume=13 |issue=1 |pages=e6 |pmid=21252034 |doi=10.2196/jmir.1643 |pmc=3221356 |doi-access=free }}</ref> Frequently, the standard of care for a particular type or stage of [[cancer]] involves the off-label use of one or more drugs. An example is the use of [[tricyclic antidepressant]]s to treat [[neuropathy|neuropathic]] [[pain]]. This old class of [[antidepressant]]s is now rarely used for [[clinical depression]] due to [[Adverse effect (medicine)|side effects]], but the tricyclics are often effective for treating pain (e.g. [[neuropathy]]),<ref>{{cite journal |title=Antidepressants in the treatment of neuropathic pain |vauthors=Sindrup SH |display-authors=etal |pmid=15910402 |volume=96 |issue=6 |date=June 2005 |journal=Basic & Clinical Pharmacology & Toxicology |pages=399–409 |doi=10.1111/j.1742-7843.2005.pto_96696601.x|doi-access=free}}</ref> as well as [[attention deficit/hyperactivity disorder]] (ADHD) particularly in adults.<ref>{{cite web |url=http://www.medscape.com/viewarticle/441910_4 |title=New Agents and Second-line Therapies for Attention-Deficit/Hyperactivity Disorder |website=Medscape}}</ref><ref>{{cite web |url=http://www.webmd.com/add-adhd/childhood-adhd/adhd-treatment-overview?page=2 |title=Treatment Options for ADHD / ADD in Children and Teens |work=WebMD}}</ref><ref>{{cite web |url=http://www.medicinenet.com/script/main/art.asp?articlekey=41885&page=2 |title=Nonstimulant Therapy (Strattera) and Other ADHD Drugs |work=MedicineNet |access-date=2015-02-03 |archive-date=2016-03-05 |archive-url=https://web.archive.org/web/20160305172151/http://www.medicinenet.com/script/main/art.asp?articlekey=41885&page=2 |url-status=dead }}</ref>