Ensuring Safe Access to Mifepristone During the Pandemic and Beyond
Authors: Beatrice L. Brown, Susan F. Wood, Ameet Sarpatwari
Journal: Annals of Internal Medicine (2020)

Ideas and OpinionsJanuary 2021Ensuring Safe Access to Mifepristone During the Pandemic and BeyondFREEBeatrice L. Brown, MBE, Susan F. Wood, PhD, and Ameet Sarpatwari, PhD, JDBeatrice L. Brown, MBEBrigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (B.L.B., A.S.), Susan F. Wood, PhDGeorge Washington University Milken Institute School of Public Health, Washington, DC (S.F.W.), and Ameet Sarpatwari, PhD, JDBrigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (B.L.B., A.S.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-6671 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Mifepristone (Mifeprex [Danco Laboratories]), 1 of 2 drugs used together to induce a medication abortion, was approved 20 years ago by the U.S. Food and Drug Administration (FDA) yet cannot be routinely prescribed and dispensed in the United States because it is covered by a risk evaluation and mitigation strategy (REMS) program. Imposed by the FDA, REMS programs are intended to minimize harms from special safety risks through such precautions as distribution controls, laboratory testing requirements, and a more robust process of informed consent. The REMS program for mifepristone is a successor to a pre-REMS restricted distribution scheme to reduce then-uncertain risks, such as major hemorrhage, from medication abortion. The program has the following 3 principal components: 1) it restricts distribution to clinics, medical offices, and hospitals; 2) it limits prescribing to certified prescribers attesting to their ability to diagnose gestational age and ectopic pregnancies, provide in-person counseling on safe use of the drug, and ensure access to surgical and medical care if needed; and 3) it requires that patients receive a special medication guide and sign an agreement acknowledging drug risks and receipt of counseling.Although many health care providers have long called for reconsideration of the mifepristone REMS program, the coronavirus disease 2019 (COVID-19) pandemic has brought new attention to the issue, in part because of the risk of in-person visits. In May, the American College of Obstetricians and Gynecologists challenged the validity of the program, arguing that it impeded access and put patients at unnecessary risk for contracting the virus. In response to the challenge, a federal court in Maryland issued a preliminary nationwide injunction preventing enforcement of the mifepristone REMS program's requirements regarding dispensing and in-person counseling for the duration of the public health emergency on the grounds that they posed an undue burden by creating a substantial obstacle without conferring significant benefit. In reaching its ruling, the court noted that the FDA had already relaxed REMS-related restrictions on distribution for esketamine (Spravato [Janssen]) and natalizumab (Tysabri [Biogen]), as well as laboratory testing and imaging requirements for all REMS programs over the same period (1).Disappointingly, the injunction has proved controversial. A month after the decision, the FDA applied for a stay to the Supreme Court, arguing that the restrictions on mifepristone do not pose an additional burden during the pandemic because surgical abortions remain available. More recently, claiming that the ruling demonstrates a movement toward deregulation and demedicalization, a group of Republican senators wrote a letter to the FDA commissioner urging him to exercise his authority to remove mifepristone from the market as an "imminent hazard to public health" (2).As these legal battles unfold during the pandemic, it is worthwhile to revisit the validity of the mifepristone REMS program and the safety of the drug itself. Multiple groups, including a study group charged with reviewing the program (3), have documented low absolute risks for adverse events with mifepristone. One review reported that major complications occurred in fewer than 1% of women who used the drug (4). In addition, women in other countries without similar restrictions on mifepristone have not experienced major harms related to the drug (3). By contrast, the REMS requirements disproportionately threaten access for low-income patients and those from rural areas.Examining the alternatives to mifepristone further bolsters the case for elimination of its REMS requirements. Guidelines from the FDA do not require a comparative safety analysis for a REMS determination (5). However, if the rationale for REMS programs is to ensure that the benefits of using a drug outweigh the risks, then alternatives to that drug—pharmacologic or otherwise—are relevant in the risk calculation. Women seeking an abortion have 2 options: a medication abortion using mifepristone, or a surgical abortion.By posing access barriers, the REMS requirements may lead women who struggle to obtain medication abortions—available through only 10 weeks of pregnancy—to seek later surgical abortions. A committee at the National Academies of Sciences, Engineering, and Medicine recently reviewed the safety and quality of abortion care. A key finding was that all methods of abortion are highly safe with only limited risks. Comparing medication versus surgical abortion in the first trimester, for example, the committee found similar risks for hemorrhage requiring blood transfusion (0.03% to 0.6% vs. 0% to 4.7%), infection (0.01% to 0.5% vs. 0% to 0.4%), and follow-up uterine aspiration (1.8% to 4.2% vs. <0.1% to 8%) (6). However, the risk for major complications from surgical abortion does increase with gestational age. One study found major complication rates of 0.16% for first-trimester surgical abortions and 0.41% for second-trimester or later procedures (7). Because the likelihood of having a surgical abortion increases once mifepristone is no longer an option, the REMS program may increase risk rather than reduce it.Political developments have added urgency to calls for elimination of the mifepristone REMS program. Several states have passed laws with no health-based rationale that threaten women's constitutional right to abortion care, such as "heartbeat bills" that ban abortion after 6 weeks of pregnancy—before many women even know that they are pregnant. Some states have also enacted targeted regulation of abortion providers (TRAP) laws, which can require an abortion provider to obtain admitting privileges at a nearby hospital and may require clinics providing surgical abortions to comply with the requirements for ambulatory surgical centers. For example, one TRAP law in Texas caused approximately half of the state's clinics to shut down before it was deemed unconstitutional by the Supreme Court in 2016 (8). Despite this ruling, other states have continued to pass TRAP laws.At the federal level, Justice Ruth Bader Ginsburg's recent death has cast into doubt the precedent built since Roe v. Wade. Barriers to contraceptive access have also been erected, which may lead to more unintended pregnancies and, thus, abortions. In March 2019, the Trump administration unveiled a domestic "gag rule" preventing facilities from receiving federal grant money for family planning and preventive health services if they provide abortion referrals. An estimated 981 clinics left the Title X network, decreasing its capacity to provide contraceptive services by at least 46% (9). Subsequently, in July 2020, the Supreme Court upheld the expansion of exemptions for religious and moral reasons to the contraceptive mandate in the Patient Protection and Affordable Care Act, which may cause between 70 500 and 126 400 women to lose contraceptive coverage (10). Under policies that may simultaneously decrease access to abortions and increase demand for the procedure, unburdened access to mifepristone can help ensure timely access to abortion care, preventing adverse health effects.The hostility toward reproductive rights in the United States also underscores the relevance of REMS messaging. During the pandemic, several states declared abortions to be "nonessential," signaling that abortion access is unimportant. Because REMS programs are mandated for drugs posing special risks, leaving any unnecessary REMS component in place suggests to women that a medication abortion is "unsafe" and could dissuade them from terminating their pregnancies using mifepristone. Given mifepristone's absolute and relative safety, continuing to keep the REMS in place resembles a value judgment rather than a factual evaluation of safety data.After 20 years of safe experience with medication abortion, it is time for the FDA to release the REMS on mifepristone. Doing so would represent a meaningful step forward for women's health and the exercise of their constitutional rights.References1. American College of Obstetricians and Gynecologists v. U.S. Food and Drug Administration. Civil action no. TDC-20-1320 (D. Md. 2020). Google Scholar2. Cruz T, Cramer K, Daines S, et al. Letter to the Honorable Stephen Hahn, MD, Commissioner of the Food and Drug Administration. 1 September 2020. Accessed at www.cruz.senate.gov/files/documents/Letters/2020.09.01%20--%20Pro-Life%20Mifeprex%20Letter%20to%20FDA%20-%20FSV.pdf on 1 September 2020. Google Scholar3. Raymond EG, Blanchard K, Blumenthal PD, et al; Mifeprex REMS Study Group. Sixteen years of overregulation: time to unburden Mifeprex. N Engl J Med. 2017;376:790-794. [PMID: 28225670] doi:10.1056/NEJMsb1612526 CrossrefMedlineGoogle Scholar4. Kapp N, Lohr PA. Modern methods to induce abortion: safety, efficacy and choice. Best Pract Res Clin Obstet Gynaecol. 2020;63:37-44. [PMID: 32029379] doi:10.1016/j.bpobgyn.2019.11.008 CrossrefMedlineGoogle Scholar5. Food and Drug Administration. Risk evaluation and mitigation strategy: the Food and Drug Administration's application of statutory factors in determining when a risk evaluation and mitigation strategy is necessary; guidance for industry; availability. Fed Regist. 2019;84 66 13668-9. Google Scholar6. National Academies of Sciences, Engineering, and Medicine. The Safety and Quality of Abortion Care in the United States. National Academies Pr; 2018. Accessed at www.nap.edu/catalog/24950/the-safety-and-quality-of-abortion-care-in-the-united-states on 17 September 2020. Google Scholar7. Upadhyay UD, Desai S, Zlidar V, et al. Incidence of emergency department visits and complications after abortion. Obstet Gynecol. 2015;125:175-83. [PMID: 25560122] doi:10.1097/AOG.0000000000000603 CrossrefMedlineGoogle Scholar8. Whole Woman's Health v. Hellerstedt, 136 S. Ct. 2292 (2016). Google Scholar9. Dawson R. Trump administration's domestic gag rule has slashed the Title X network's capacity by half. Guttmacher Institute. 5 February 2020. Accessed at www.guttmacher.org/article/2020/02/trump-administrations-domestic-gag-rule-has-slashed-title-x-networks-capacity-half on 17 September 2020. Google Scholar10. Internal Revenue Service; Employee Benefits Security Administration; Centers for Medicare & Medicaid Services. Religious exemptions and accommodations for coverage of certain preventive services under the Affordable Care Act. Fed Regist. 2018;83 221 57536-90. MedlineGoogle Scholar Comments0 CommentsSign In to Submit A Comment Claudio L.Urosa M D FACP1.Centro médico de Caracas 2 .Bioethics Commitee Hospital Universitario de Caracas22 October 2020 "Safe access to Mifepristone during the pandemic" Regarding ensuring "Safe access to mifepristone during the pandemic and beyond", it is very important to remark the fact that besides the risks of hemorrhage and infection for the women taking the drug, is the is the 100% risk of death for the unborn human embrio. We know that from the very begining of pregnancy a new human life is present. For the above reason I discourage the aproval of Mifepristone to induce "medical abortion"as any other means to destroy a human life. Claudio L. Urosa M D FACP . Venezuela Governor Elect 2021-2025 Richard HardinSelf21 October 2020 Abortion Forgive my ignorance, but where in the constitution does it say that women should have access to abortion? Nassim AssefiInternist and global health physician22 October 2020 Mifepristone Should Be Treated as a Normal Medication I wholeheartedly agree with the Annals Op-Ed on normalizing mifepristone access in the US. Anti-abortion politics notwithstanding (of which there are also representatives among physicians), there is no medical reason to dispense this medication only in-person under the REMS protocol. I've personally had much clinical experience with mifepristone since 20 years ago when it became legal in the US, have read the global studies showing how safe medical abortion is via telemedicine, and am aghast by how much political interference and misogyny obstruct US women's access to safely terminate a pregnancy. Most Americans support Roe v. Wade; even more physicians believe in a woman's right to choose abortion. Let's not allow personal politics to interfere with sound medical logic. I applaud the Annals of Internal Medicine for addressing this fundamental issue in women's health. May we not be cowed by a vocal minority who wish to impose their own religious and moral beliefs on others, and stand up for what the science says. Eleanor Schwarz, MD, MS, FACPUC Davis22 October 2020 Mifepristone Training Given the prevalence of early pregnancy loss and abortion, mifepristone is an important medication for primary care clinicians to be familiar with. Training on use of this medication in primary care practice is available at https://abortionpillcme.teachtraining.org/ Ted PalenMember of the Christian Medical and Dental Associations21 October 2020 Mifepristone is not low risk The authors state that mifepristone has a "low absolute risks for adverse events." I would strong differ. For every use of this drug one person dies, the pre-born baby. So I would say this drug carries a risk of 100% for harm. Abortion advocates always seem to forget there are two patients involved in every abortion, and one dies. Mark Antony LaPorta MD FACPMark Antony LaPorta MD FACP26 October 2020 Writer's credentials I find it noteworthy that none of the authors are physicians or clinicians. This whole issue -- abortion rights and access -- has been debated in drips and drabs for how many decades, and sometimes we come to temporary agreement on some of its facets. No wholistic resolution is in sight. NO intervention is without risks, alternatives, and imponderables. This is not a partisan matter. SPoppema, MDMD International Consulting27 October 2020 Wholeheartedly agree The need to improve access to mifepristone is critical. Medication abortion, self-managed is extremely safe as has been shown in multiple studies. Especially in this time of COVID we must do all we can as physicians to prevent our patients from being trapped into pregnancy slavery. I fully agree with the authors. Author, Article, and Disclosure InformationAffiliations: Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (B.L.B., A.S.)George Washington University Milken Institute School of Public Health, Washington, DC (S.F.W.)Acknowledgment: The authors thank Aaron Kesselheim, MD, JD, MPH, for his comments on an earlier draft.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-6671.Corresponding Author: Ameet Sarpatwari, PhD, JD, 1620 Tremont Street, Suite 3030, Boston, MA 02120; e-mail, [email protected]harvard.edu.Current Author Addresses: Ms. Brown and Dr. Sarpatwari: 1620 Tremont Street, Suite 3030, Boston, MA 02120.Dr. Wood: 950 New Hampshire Avenue NW, Washington, DC 20052.Author Contributions: Conception and design: B.L. Brown, A. Sarpatwari.Analysis and interpretation of the data: B.L. Brown, S.F. Wood, A. Sarpatwari.Drafting of the article: B.L. Brown, A. Sarpatwari.Critical revision of the article for important intellectual content: B.L. Brown, S.F. Wood, A. Sarpatwari.Final approval of the article: B.L. Brown, S.F. Wood, A. Sarpatwari.Administrative, technical, or logistic support: B.L. Brown, A. Sarpatwari.Collection and assembly of data: B.L. Brown.This article was published at Annals.org on 21 October 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byState Restrictions on Mifepristone Access — The Case for Federal PreemptionMiles and days until medical abortion via TelAbortion versus clinic in Oregon and Washington, USAClinical Efficacy and Safety Study of Mifepristone with Misoprostol Treatment in Patients with Missed AbortionThe perspective of Canadian health care professionals on abortion service during the COVID-19 pandemicFactors associated with successful implementation of telehealth abortion in 4 United States clinical practice settings January 2021Volume 174, Issue 1Page: 105-106 ePublished: 21 October 2020 Issue Published: January 2021 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...