Posts Tagged ‘abortion’
Volume 41, Issue 1 (2023)
Proscribing Prescriptions: A Legal Analysis of State Off-Label Restrictions on Medication Abortion
by Kaiya A. Lyons
Since its decision in Roe v. Wade, the Supreme Court has consistently upheld the right of a woman to choose to terminate a pregnancy before viability and without undue burden. However, the ability of a woman to exercise that right today is as intimately connected to her economic privilege and geographic location as it was in the days preceding that landmark ruling. Under the guise of protecting women from the “harms inherent in abortion,” major conservative gains in the 2010 midterm elections resulted in hundreds of anti-abortion measures flooding a majority of state legislatures. In the aftermath of that year’s midterm elections, the bulk of state legislatures passed an unprecedented number of harsh new restrictions on when, how, and even whether women may access abortion services. Because these laws are also substantially more obstructive than their predecessors, for low-income women, the economic impact of these restrictive regulations is extremely harmful.
One of the most harmful and least publicized forms of these restrictions is state regulation of the administration of medication abortion drugs. The Food and Drug Administration (FDA) first approved the use of medication to perform abortions in 2000. Since the advent of this nonsurgical option, 41% of all first-trimester abortions performed by Planned Parenthood clinics nationwide are now conducted using a combination of two prescription drugs, mifepristone (sometimes referred to as RU-486) and misoprostol. When properly administered, medication abortion is exceptionally safe—even more so than surgical abortions, which are especially safe in their own right. Twenty years of studies on the safety and effectiveness of medication abortion have shown no long-term risks associated with the method. In fact, contrary to state laws that suggest abortions are high-risk procedures, at least one study demonstrates that early surgical abortions are safer than giving birth.
Despite the demonstrably low risk involved in the procedure, a majority of states have enacted restrictions on women’s ability to access medication abortion, including “limitations on the types of health care providers who can give women the pills, prohibitions on prescribing the pills remotely (through telemedicine)[,] and bans on home self-administration.” Thirty-seven states currently require a licensed physician to provide the pills, preventing over-the-counter or pharmacy access to medication abortion drugs; nineteen of those states further require the physician to be in the physical presence of the patient when acquiring a prescription for the drugs, essentially prohibiting the use of telemedicine.
However, six states have taken a discreetly radical stance against the method by attempting to require healthcare providers to adhere to an outmoded FDA procedure for administering mifepristone, known as the “on-label regimen[,]” for its placement on the drug’s packaging. Based on the “most published clinical evidence” available at the time, this initial on-label regimen required a woman seeking a medication abortion to make three visits to a clinic within the first seven weeks after fertilization in order to terminate her pregnancy. During the first visit, the woman would take 600 milligrams of mifepristone orally; two days later, during the second visit, she would take 400 micrograms of misopristol orally in the presence of a healthcare provider; and finally, she had to visit the clinic a third time for a follow-up appointment to verify the success of the abortion.
Although clinical trials had originally shown this on-label regimen to be safe, “[a] large body of research has [since] developed on alternative dosages of the drugs and timing and route of administration to improve success rates for medication abortion.” In fact, while the FDA was reviewing the on-label regimen, studies were already revealing a safer, more effective technique for administering mifepristone. Known as the “evidence-based regimen,” this new technique not only requires a lower dosage of the drug—thus reducing the risk of hemorrhage—but it also entails only two trips to the clinic, made within nine weeks of pregnancy.
Based on this information, medical professionals soon began administering medication abortion according to this safer regimen—a practice known as “off-label” prescribing. One year after the FDA first approved the use mifepristone, the vast majority of healthcare providers had already rejected the agency’s protocol in favor of the less risky and more affordable evidence-based regimen. This modification in care decreased the costs, the number of clinic visits, and health risks associated with medication abortion, consequently expanding abortion access to women for whom the on-label regimen had been exceedingly cost prohibitive and time consuming.
Abortion providers’ transition to the evidence-based regimen was not a particularly revolutionary maneuver. Prescribing drugs “off-label” is a commonplace and often-necessary practice, supported by the medical community, which can be a life-saving standard of care in cases of serious illnesses and cancer. The practice is extremely common among physicians, and professional medical organizations agree that off-label prescribing may be the best practice in some instances. Indeed, an estimated 25–60% of all prescriptions written in the United States are for off-label uses. Moreover, national medical associations have approved of the practice, articulating their opinion that physician discretion in the provision of medical care is of the utmost importance to the efficacy of the medical field and the promotion of patient health.
Off-label prescribing is not only commonplace, but it is also entirely legal. While the FDA governs the approval of pharmaceutical drugs, it does not regulate the practice of medicine, including the manner of administering prescription drugs. In fact, the FDA has recognized that off-label prescribing may be the optimal standard of care for certain conditions. Therefore, physicians have autonomy to prescribe those drugs approved by the FDA based on their medical judgment, subject to malpractice and informed consent laws. However, as the reproductive rights community has learned, this administrative scheme has not prevented state law from prohibiting the practice in the context of medication abortion. Indeed, the discrepancy between the FDA label and medical practice gave rise to off-label prescription restrictions as a quiet, yet powerful, tactic in anti-choice lawmakers’ incremental approach to abortion regulation.
Regardless of the demonstrated effectiveness, safety, and general popularity of the evidence-based regimen, six states have attempted to require providers to adhere to the outdated and harmful on-label regimen approved by the FDA in 2000. Although courts have either permanently or temporarily enjoined off-label restrictions in Arizona, Arkansas, and Oklahoma, laws requiring abortion providers to adhere to the protocol authorized by the FDA are still in effect for women in North Dakota, Ohio, and Texas. Not surprisingly, these prohibitions are unique state legislative actions because they are in direct contrast to health care professionals’ best medical judgments and they can have deleterious impacts.
The Ninth Circuit’s 2014 decision in Planned Parenthood of Arizona v. Humble provides an example of the disproportionately negative effects state on-label requirements have on low-income women. In 2012, the Arizona state legislature approved several amendments to its abortion regulations, including a requirement that physicians prescribe medication abortion “in compliance with the protocol that is authorized by the [FDA] and that is outlined in the final printing labeling instructions for that medication.” Defending the provision, the Arizona legislature maintained that the requirement would “[p]rotect women from the dangerous and potentially deadly off-label use of abortion-inducing drugs, such as, for example, mifepristone.” However, the Ninth Circuit in Humble disagreed and affirmed a District Court finding that the evidence-based regimen was scientifically more advantageous to the health and safety of Arizona women.
As the Ninth Circuit noted, under the on-label regimen, women are required to ingest higher doses of mifepristone, subjecting as many as 8% of women to subsequent surgical abortion procedures due to either heavy bleeding caused by the over dosage of the medication or failure to terminate the pregnancy. Comparatively, fewer than 2% of women following the evidence-based regimen require such subsequent medical treatment. In addition to the risk of future ameliorative surgical measures, the increased dosage and clinic visits involved in the on-label regimen significantly increased the cost of the procedure in comparison to that of the evidence-based regimen, “reduc[ing] the number of women who receive abortions, many of whom . . . are poor.” Thus, through a confluence of factors—including multiple visits to clinics, increased costs, and an escalated risk of failure to terminate the pregnancy—such regulations made medication abortion an unpredictable and potentially hazardous option for low-income women in Arizona.
For women in Arizona, the Ninth Circuit’s opinion in Humble fortunately prevented the law from taking effect. However, in several states, off-label restrictions remain good law. Take, for example, the Ohio provision requiring physicians to administer mifepristone to satisfy “all the criteria established by federal law.” Unlike other attempted on-label restrictions that have been enjoined by court order, because the Ohio law is still in effect, researchers from Advancing New Standards in Reproductive Health (ANSIRH) at the University of California San Francisco were able to study the real impact off-label restrictions have on the health of women seeking medication abortions. In a recently-published article summarizing their research, the team compared the outcomes of Ohio patients pre- and post-law to determine the effects of the on-label regimen. The findings provide further evidence that such regulations harm, rather than advance, women’s health and economic stability. Compared to the outcomes of women receiving evidence-based care, women receiving on-label care were three times as likely to need additional intervention to complete the abortion. Moreover, post-law patients experienced more clinic visits, more side effects (including nausea and vomiting), and higher costs in procuring their medication abortions than pre-law patients.
Thankfully, many of the negative impacts of such off-label restrictions have been halted for the time being. In March 2016, the FDA updated the on-label instructions for the provision of mifepristone to reflect the evidence-based regimen commonly used in practice. The new label conforms to the evidence-based regimen by “reducing the dosage to 200 milligrams from 600 milligrams, decreasing the number of visits a woman must make to a doctor to two from three, and extending the period when she can take the pill to 10 weeks of pregnancy from seven weeks.” This regulatory change is good news for women’s health clinics in states with off-label restrictions, where providers may now legally prescribe medication abortion according to the evidence-based regimen.
However, new research always has the potential to improve clinical best practices. Indeed, that is the point of such clinical trials. Therefore, it is possible—if not inevitable—that women in Ohio, North Dakota, and Texas will no longer be legally entitled to the most up-to-date reproductive health care in the near future. This is especially worrisome for pro-choice advocates in light of current clinical trials testing the safety of pharmacy access to medication abortion, which would increase access to the drugs to women in remote areas of the country. If these trials are successful, the current FDA requirement that health care providers must dispense mifepristone in a clinic, medical office, or hospital would be outdated. Not only would this discrepancy in regulation and clinical best practices affect the three existing off-label restriction states, but it would also controvert the laws of thirty-seven states that currently require licensed physicians to provide medication abortion drugs.
Even if the FDA responded to such evidence by updating its mifepristone prescription regimen and recommendations once again, conservative states may have a legislative fail-safe up their proverbial sleeves. A real-life example of this tactic, one day after the FDA updated its mifepristone protocol, the Arizona state legislature inserted a rider to a bill regarding pharmacies and vaccinations to revise its abortion statute. If successful, this rider would have limited the provision of mifepristone to the “final printing label protocol that [was] approved by the United States food and drug administration and in effect as of December 31, 2015.” Although legislators eventually struck this backdating language before final passage of the bill, Arizona’s overt attempt to circumvent the FDA signified a disquieting new anti-abortion strategy for conservative state legislatures. By nearly succeeding in exploiting this potential legislative loophole, Arizona further demonstrates that as long as women’s health clinics are “required to provide care based on legislation, rather than the most up-to-date research and evidence-based practice,” access to essential health care will continue to be dependent upon a woman’s zip code and privilege.
 J.D., University of Minnesota Law School, 2016; B.A., The George Washington University, 2013. Portions of this article were previously published in the Thurgood Marshall School of Law Journal on Gender, Race, and Justice. Kaiya A. Lyons, The Interstate Commerce of Abortion: A Constitutional Argument for the Federal Invalidation of Restrictive State Abortion Laws, 6 T. Marshall L.J. Gender, Race, & Just. 56 (2016).
 See Planned Parenthood of Central Missouri v. Danforth, 428 U.S. 52 (1976); Beal v. Doe, 432 U.S. 438 (1977); Maher v. Roe, 432 U.S. 464 (1977); Poelker v. Doe, 432 U.S. 519 (1977); Bellotti v. Baird, 443 U.S. 622 (1979); Harris v. McRae, 448 U.S. 297 (1980); Simopoulos v. Virginia, 462 U.S. 506 (1983); Webster v. Reprod. Health Servs., 492 U.S. 490 (1989); Planned Parenthood of Southeastern Pennsylvania v. Casey, 505 U.S. 833, 846 (1992) (“[T]he essential holding of Roe v. Wade should be retained and once again reaffirmed.”); Stenberg v. Carhart, 530 U.S. 914 (2000); Gonzalez v. Carhart, 550 U.S. 124 (2007); Whole Women’s Health v. Hellerstedt, 579 U.S. ___ (2016).
 Eric Eckholm, Access to Abortions Falling as States Pass Restrictions, N.Y. Times (Jan. 3, 2014), http://www.nytimes.com/2014/01/04/us/women-losing-access-to-abortion-as-opponents-gain-ground-in-state-legislatures.html.
 See Mailee R. Smith, 2013 State Legislative Sessions: Unabashedly Pro-Life and Pro-Woman, in 17 Defending Life 2013: Deconstructing Roe: Abortion’s Negative Impact on Women
(Americans United for Life ed., 2014), http://www.aul.org/wp-content/uploads/2014/03/2013-State-Legislative-Sessions-Unabashedly-Pro-Life-and-Pro-Woman-DL-2014.pdf.
 As a result of the 2010 midterm elections, the Tea Party and GOP controlled twenty-six state legislatures. Janet Reitman, The Stealth War on Abortion, Rolling Stone (Jan. 15, 2014), http://www.rollingstone.com/politics/news/the-stealth-war-on-abortion-20140115#ixzz2r9Rwp7PA. For a discussion of the 2010 midterm election’s effects on the antiabortion movement, see Angela Hooton & Aram Schvey, 50 States of Denial: States Deny Women Reproductive Rights, 40 Hum. Rts. 15, 15–16 (2014); John A. Robertson, Abortion and Technology: Sonograms, Fetal Pain, Viability, and Early Prenatal Diagnosis, 14 U. Pa. J. Const. L. 327, 330 (2011); Erik Eckholm, Across Country, Lawmakers Push Abortion Curbs, N.Y. Times, Jan. 22, 2011, at A1.
 Heather D. Boonstra & Elizabeth Nash, A Surge of State Abortion Restrictions Puts Providers-And the Women They Serve-in the Crosshairs, 17 Guttmacher Pol’y Rev. 9, 9 (2014). In fact, the record-breaking number of state antiabortion regulations enacted since 2011 substantially exceeds the total number of similar measures passed throughout the previous decade. See id.; Tara Culp-Ressler, In the Past 3 Years, We’ve Enacted More Abortion Restrictions Than During the Entire Previous Decade, ThinkProgress (Jan. 2, 2014), http://thinkprogress.org/health/2014/01/02/3112081/abortion-restrictions-2011-2013.
 Hooton & Schvey, supra note 5, at 17 (“We know that for low-income women in particular, the economic impact of abortion restrictions can be extremely harmful”); Boonstra & Nash, supra note 6, at 13 (“Unquestionably, abortion restrictions fall hardest upon the poorest women, the very group bearing a disproportionate burden of unintended pregnancies.”).
 Stanley K. Henshaw & Lawrence B. Finer, The Accessibility of Abortion Services in the United States, 2001, 35(1) Perspectives on Sexual and Reproductive Health 16, 20 (2003), https://www.guttmacher.org/sites/default/files/pdfs/journals/3501603.pdf.
 Planned Parenthood of Arizona, Inc. v. Humble, 753 F.3d 905, 908 (9th Cir. 2014).
 Susan Dudley & Beth Kruse, Safety of Abortion, Nat’l Abortion Fed’n (Dec. 2006), http://prochoice.org/wp-content/uploads/safety_of_abortion.pdf.
 Genevra Pittman, Abortion Safer Than Giving Birth: Study, Reuters (Jan. 23, 2012, 5:16 PM), http://www.reuters.com/article/us-abortion-idUSTRE80M2BS20120123 (citing Elizabeth Raymond & David Grimes, The Comparative Study of Legal Induced Abortion and Childbirth in the United States, 119 Obstetrics & Gynecology 215, 216 (2012)).
 See Medication Abortion: State Policies in Brief, Guttmacher Inst. (Oct. 1, 2016), https://www.guttmacher.org/print/state-policy/explore/medication-abortion (providing a frequently updated record of state medication abortion laws) [hereinafter Medication Abortion].
 Ushma D. Upadhyay, We Need Abortion Laws Based on Science, N.Y. Times (Aug. 30, 2016), http://www.nytimes.com/2016/08/31/opinion/how-abortion-pill-laws-hurt-women.html?_r=1.
 Medication Abortion, supra note 13.
 Id. See Ariz. Rev. Stat. Ann. § 36-449.03(E)(6) (2012), temporarily enjoined by Planned Parenthood of Arizona v. Humble, 753 F.3d 905 (9th Cir. 2014); Ark. Code Ann. § 20-16-1504(a)(2) (West 2016), temporarily enjoined by Planned Parenthood Arkansas & Eastern Oklahoma v. Jegley, No. 4:15-cv-00784-KGB (E.D. Ark., Mar. 14, 2016); N.D. Cent. Code § 14-02.1-03.5 (West 2011); Ohio Rev. Code Ann. § 2919.123 (West 2004); Okla. Stat. Ann. tit. 63, § 63-1-729a (West 2014), permanently enjoined by Oklahoma Coalition for Reproductive Justice v. Cline, 292 P.3d 27 (Okla. 2012); Tex. Health & Safety Code Ann. § 171.063(a)(2) (West 2013).
 Ushma D. Upadhyay et al., Comparison of Outcomes Before and After Ohio’s Law Mandating Use of the FDA-Approved Protocol for Medication Abortion: A Retrospective Cohort Study, PLOS Med. 3 (2016), http://journals.plos.org/plosmedicine/article/asset?id=10.1371/journal.pmed.1002110.pdf [hereinafter Comparison of Outcomes].
 Henshaw & Finer, supra note 8, at 20.
 Humble, 753 F.3d at 907.
 Comparison of Outcomes, supra note 17, at 3.
 Humble, 735 F.3d at 907–08 (“This regimen requires taking 200 milligrams (instead of 600 milligrams) of mifepristone orally at the clinic, taking 800 micrograms of misoprostol two days later at home (instead of at the clinic) by dissolving the drug between the cheek and gum, and then returning to the clinic for a follow-up visit.”).
 Off-label prescribing can occur in three ways: “(1) prescribing for unapproved conditions, (2) prescribing for patient groups other than those approved, and (3) varying the dosage or method of administering a drug.” Amy E. Todd, No Need for More Regulation: Payors and Their Role in Balancing the Cost and Safety Considerations of Off-Label Prescriptions, 37 Am. J. L. & Med. 422, 424 (2011).
 Henshaw & Finer, supra note 8, at 20–22.
 See We Need Abortion Laws Based on Science, supra note 14.
 See Brief for American College of Obstetricians & Gynecologists & the American Medical Association as Amici Curiae Supporting Plaintiffs-Appellants at 15, Planned Parenthood of Arizona, Inc. v. Humble, 753 F.3d 905 (9th Cir. 2014) [hereinafter Brief of Amici Curiae]; Mark Herrman & Pearson Bownas, Keeping the Label Out of the Case, 103 Nw. U. L. Rev. Colloquy 477, 479 (2009) (estimating that 65% of cancer patients, 70% of kidney dialysis patients, and 80% of AIDS patients receive off-label treatment).
 Policy H-120.988, Patient Access to Treatments Prescribed by Their Physicians, Am. Med. Ass’n, https://www.regulations.gov/contentStreamer?documentId=FDA-2008-D-0053-0031&attachmentNumber=2&disposition=attachment&contentType=pdf (confirming the AMA’s strong support for the proposition that “a physician may lawfully use an FDA approved drug product or medical device for an off-label indication when such use is based upon sound scientific evidence and sound medical opinion”).
 Laurah J. Samuels, Mifepristone Protocol Legislation – The Anti-Choice Movement’s Disingenuous Method of Attack on the Reproductive Rights of Women and How Courts Should Respond, 26 Colum. J. Gender & L. 316, 321 (2014) (citing Dov Fox, Safety, Efficacy, and Authenticity: The Gap Between Ethics and Law in FDA Decisionmaking, 2005 Mich. St. L. Rev. 1135, 1160 (2005)); see also Emily Bazelon, The Cleverest New Anti-Abortion Law, Slate (Sept. 10, 2013, 5:15 PM), http://www.slate.com/articles/news_and_politics/jurisprudence/2013/09/oklahoma_and_mifiprex_supreme_court_considers_law_about_fda_approved_medical.html (“The American Medical Association estimates that one-half of all prescriptions written are off-label.”).
 See Brief of Amici Curiae, supra note 25; Statement of Policy: Legislative Interference with Patient Care, Medical Decisions, and the Patient-Physician Relationship, Am. Cong. of Obstetricians & Gynecologists (May 2013), http://www.acog.org/~/media/Statements%20of%20Policy/Public/2013LegislativeInterference.pdf.
 Carol R. Berry, The Dividing Line Between the Role of the FDA and the Practice of Medicine: A Historical and Current Analysis 2–10 (1997) (unpublished Third Year Paper, Harvard Law School), http://dash.harvard.edu/bitstream/handle/1/8846812/cberry.pdf?sequence=1.
 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), 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.”).
 Todd, supra note 22, at 424.
 Tara Culp-Ressler, The FDA Just Removed One of Anti-Abortion Lawmakers’ Favorite Talking Points, ThinkProgress (Mar. 30, 2016), https://thinkprogress.org/the-fda-just-removed-one-of-anti-abortion-lawmakers-favorite-talking-points-82bb58a6eb7d#.kfwp2jmz6.
 Medication Abortion, supra note 13.
 Id. See also supra note 16.
 753 F.3d 905, 914–18 (9th Cir. 2014) (reversing and remanding a district court’s denial of plaintiff’s motion for a preliminary injunction and holding that plaintiffs have shown a likelihood of success on their claim that the Arizona law imposes an undue burden on a woman’s right to abortion). Contra Planned Parenthood Sw. Ohio Region v. DeWine, 696 F.3d 490, 513–18 (6th Cir. 2012) (holding that the Ohio statute adhering to the FDA on-label regimen did not impose an undue burden on a woman’s ability to decide to have an abortion).
 H.B. 2036, 50th Leg., 2d Sess. (Ariz. 2012).
 Humble, 735 F.3d at 910.
 Id. at 908 (quoting the lower court’s finding that “there is a clear advantage to the current protocol because it may be used through the 9th week of pregnancy . . . which is significant because many women do not discover their pregnancies until approximately 49 days, which is the end of [the] 7th week . . . . Also, risk factors from medical abortions . . . have been reduced or eliminated by the current [evidence-based] regimen.”).
 Id. (quoting the lower court’s finding that in “[t]he evidence-based regimen . . . fewer than 2 percent of women require subsequent surgical-abortion procedures).
 Id. at 916. The Ninth Circuit further noted that the the additional costs of the regimen were “significant and sometimes prohibitive.” Id. at 908, 916.
 Ohio Rev. Code Ann. § 2919.123(A) (West 2004). See also id. at § 2919.123(F)(1) (defining “federal law” as “any law, rule, or regulation of the United States or any letter of the food and drug administration of the United States that governs or regulates the use of RU-486 (mifepristone) for the purpose of inducing abortions”).
 Comparison of Outcomes, supra note 17.
 Id. at 5–8.
 Id. at 16–19.
 Id. at 3, 9.
 Id. at 3.
 Sabrina Tavernise, New F.D.A. Guidelines Ease Access to Abortion Pill, N.Y. Times (Mar. 30, 2016), http://www.nytimes.com/2016/03/31/health/abortion-pill-mifeprex-ru-486-fda.html.
 U.S. Nat’l Inst. Health, Learn About Clinical Studies, ClinicalTrials.gov, https://clinicaltrials.gov/ct2/about-studies/learn (last visited Oct. 24, 2016).
 See We Need Abortion Laws Based on Science, supra note 14.
 Mifeprex (Mifepristone) Information, U.S. Food & Drug Admin., http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111323.htm (last visited Oct. 24, 2016).
 Medication Abortion, supra note 13.
 2016 Ariz. S.B. 1112 § 4(E)(6) (Apr. 20, 2016 version) (showing the relevant rider language struck from the statute).
 Id.; see also Erik Eckholm, Gov. Doug Ducey of Arizona Signs Abortion Drug Bill that Skirts New F.D.A. Protocol, N.Y. Times (Apr. 1, 2016), http://www.nytimes.com/2016/04/02/us/gov-doug-ducey-of-arizona-signs-abortion-drug-bill-that-skirts-new-fda-protocol.html.
 See 2016 Ariz. S.B. 1112 § 4(E)(6), supra note 55.
 Comparison of Outcomes, supra note 17, at 3.