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Oklahoma's Restrictions on the Use of RU-486 Follow FDA Restrictions

JURIST Guest Columnist Mailee R. Smith of Americans United for Life discusses how the Supreme Court should rule in Cline v. Oklahoma Coalition for Reproductive Justice...

The US Supreme Court has never reviewed a regulation of chemical abortion—and now that it might in Cline v. Oklahoma Coalition for Reproductive Justice, many in the "chattering classes," including the media, are racing to offer opinions as to the implications of the groundbreaking 2011 Oklahoma regulation at issue in the case, a law that originated from Oklahoma House Bill 1970. Unfortunately, many of these opinions are not based in reality, such as allegations that off-label uses of abortion-inducing drugs (such as the RU-486 regimen) are safer for women than following FDA-approved protocols, or that Oklahoma is attempting to ban all chemical abortions. The facts—and the law—tell a much different story.

The Facts

The US Food and Drug Administration (FDA) has approved only one drug regimen for women seeking chemical (i.e., non-surgical) abortions. The FDA-approved regimen actually involves two drugs: mifepristone (brand name Mifeprex, commonly referred to as RU-486) and misoprostol. In all FDA materials—as well as the Mifeprex label—the two drugs are linked together as one regimen. There is no other protocol approved by the FDA. Two drugs, one regimen, with the Mifeprex label providing the only instance of instructional protocol for the use of both drugs.

When the FDA approved the regimen, it did so under a special code section known as "Subpart H." Subpart H is an approval process used for drugs that "can be safely used only if distribution or use is restricted." Under Subpart H, the FDA can "require such postmarketing restrictions as are needed to assure safe use" of the drug approved. To put this in perspective, out of almost 1,800 new drug applications (NDAs) approved between 1992 and 2011, only 70 were approved under the provision.

Subpart H approvals are rare, and these drugs are treated differently than the vast majority of drugs approved under regular FDA processes. In its September 2000 letter approving the RU-486 regimen, the FDA reiterated that Subpart H restrictions apply when it concludes that a drug can be safely used only if its distribution or use is controlled to protect the safety of its users. So when abortion proponents argue that the FDA allows and approves of off-label drug use, they are completely ignoring the fact that the FDA has never treated the RU-486 drug regimen like just another routine other drug.

FDA restrictions on the RU-486 regimen include that a qualified physician supervise its distribution. For example, the physician must be able to assess the duration of pregnancy (because risk from chemical abortion increases with gestational age) and diagnose ectopic pregnancies (which cannot be treated by RU-486, and left untreated can lead to fallopian tube rupture and death). Further, both the patient and the physician must sign an agreement stating that the patient is not more than 49 days pregnant and that she will return to the physician's office to take misoprostol, the second drug in the approved regimen.

This required written agreement completely undercuts abortion proponents' claim that the FDA did not intend for physicians to follow a certain protocol when providing the RU-486 regimen. Not only did the FDA approve the drug under the only code section that allows it to restrict the use of certain drugs, but it requires that physicians and patients both sign a statement that they are adhering the FDA-approved protocol.

The FDA's intent to restrict the use of the RU-486 regimen is also documented in a Department of Health and Human Services (HHS) report issued simultaneously with the approval of the RU-486 regimen. In the Memorandum of Department of Health and Human Services to "NDA 20-687 MIFEPREX (mifepristone) Population Counsel," HHS reported that the FDA identified "compliance with the regimen" as contributing to drug safety and effectiveness. HHS also relayed that the Medication Guide accompanying the drugs—which, among other things, instructs women not to use the regimen past 49 days and to return to the office on day 3 to receive misoprostol (i.e., not to self-administer alone at home)—would help "enhance compliance with the regimen for safety and efficacy." In fact, HHS stated that returning to a physician's office on day 3 for misoprostol is "a requirement" that assures correct administration, and that "goals of safe and appropriate use" of the drugs can be achieved through the drug labeling—i.e., following the FDA-approved protocol in the drug label.

However, abortion providers persist in administering the drugs in a dangerous and unapproved manner. Notably, women are given the drugs outside the 49-day gestational limited imposed by the FDA, women are sent home to self-administer misoprostol without any medical supervision and women are told to use misoprostol vaginally or buccally (and not orally, as the FDA approved).

Proponents of this off-label use claim it is somehow safer, but offer no medical evidence to substantiate their claims. In not one case—including Cline—have abortion proponents introduced any peer-reviewed evidence supporting their speculation that it is safer to administer abortion-inducing drugs in ways not approved by the FDA.

On the other hand, reports of complications from the use of the RU-486 regimen have poured into the FDA. Between 2000 and 2011, the FDA received reports of over 2,200 complications, many of which were severe. Fourteen women had died by 2011. Eight of these women died of bacterial infections, and in all eight cases the women had administered misoprostol either vaginally or buccally—not orally as instructed by the FDA. Importantly, the FDA issued a public safety warning in 2006, reiterating the proper protocol for the approved Mifeprex regimen.

Of course, some of these complications were not unexpected. When the FDA approved the regimen in 2000, the Mifeprex label acknowledged that nearly all women administering the regimen will experience adverse events, with many women experiencing more than one.

Moreover, a 2008 report [PDF] by the Government Accountability Office revealed that "FDA officials have concluded that, with the exception of the cases of fatal infection, the reported serious adverse events associated with Mifeprex have been within or below the ranges expected."

On its face, this is a fairly damning statement. In 2008, we did not yet know that as many as eight women had died from bacterial infections. And not only does this GAO admission indicate that the FDA expected nearly all women utilizing chemical abortion to experience complications—something that should concern every women considering chemical abortions—but it also means that abortion proponents are pushing a drug regimen that has yielded more deaths from bacterial infection than the FDA expected.

While abortion proponents have not a single peer-reviewed study supporting their claim that an off-label regimen is safer than the FDA-approved protocol, there is evidence that surgical abortion is safer than chemical abortion. One study revealed that the overall incidence of immediate adverse events is fourfold higher for chemical abortions than for surgical abortions. Another study reported that chemical abortion failed in 18.3 percent of patients (meaning that women must go through a second abortion procedure) and that surgical abortion failed in only 4.7 percent of patients. In that study, patients undergoing chemical abortions reported significantly longer bleeding and higher levels of pain, nausea, vomiting, and diarrhea than women who chose surgical abortions.

In sum, abortion proponents rely on no evidence or medical data when challenging abortion-inducing drugs regulations. Conversely, the FDA continues to endorse the 2000 approved protocol. Eight women have died from severe bacterial infection following misuse of the RU-486 regimen. The FDA has not determined that misuse caused these deaths, but it has also not been able to determine that the misuse did not cause them.

In light of the medical uncertainty as to what actually caused these women's deaths, states should step in to protect women considering chemical abortions.

The Law

This brings us to Oklahoma. Desiring to protect women from the potentially deadly risks involved with off-label administration of the RU-486 regimen, state legislators sought to proscribe this misuse by requiring that abortion providers abide by the FDA-approved protocol delineated in the regimen's labeling. Specifically, the regulation requires that physicians administer the drugs as "authorized by the [US] Food and Drug Administration and as authorized in the drug label for the RU-486 (mifepristone)." The regulation also applies to other abortion-inducing drugs. This means that physicians cannot administer the drugs when a woman's pregnancy exceeds 49 days, and that the woman must return to the office or clinic for the second drug in the regimen, misoprostol, the use of which is described in the FDA-approved label, in the patient agreement, and in the HHS memo.

Importantly, US Supreme Court precedent supports the Oklahoma regulation. In both Planned Parenthood v. Casey andGonzales v. Carhart, the Court affirmed Roe v. Wade's "essential" holding, which specifically included "the principle that the [s]tate has legitimate interests from the outset of pregnancy in protecting the health of the woman." This principle must "coexist" with other principles outlined in Roe. Thus, instead of supporting such "zero tolerance policies" as had been applied to some abortion regulations in the past, the court in Casey utilized an undue burden standard, examining whether a state regulation had the purpose or effect of placing a substantial obstacle in the path of a woman seeking an abortion of a non-viable fetus.

Gonzales expanded on the applicability of this undue burden standard to the regulation of pre-viability abortions. The court explained that state and federal legislatures are given "wide discretion to pass legislation in areas where there is medical and scientific uncertainty." Importantly, the court concluded that "[p]hysicians are not entitled to ignore regulations that direct them to use reasonable alternative procedures. The law need not give abortion doctors unfettered choice in the course of their medical practice." If a particular regulation still allows "a commonly used and generally accepted method" of abortion, it does not construct a substantial obstacle to the abortion "right."

Thus, the Oklahoma regulation is overwhelmingly supported by US Supreme Court precedent. The medical uncertainty surrounding the potentially deadly effects of off-label use—and the FDA's intent to regulate the drugs and abortion proponents' inability to muster even a single peer-reviewed study demonstrating safety data for their off-label use—place the regulation within the "wide discretion" of the state legislature. The Oklahoma regulation does not prohibit all chemical abortions, nor does it even touch upon surgical abortion—a procedure deemed "very safe" by the abortion industry and utilized in the majority of first-trimester abortions. As such, a "commonly used and generally accepted method" of abortion is accessible to women in Oklahoma.

Instead of granting full review of the regulation, the US Supreme Court has asked the Oklahoma Supreme Court to interpret the regulation (a role the state supreme court failed to undertake the first time in its cursory three-paragraph opinion) and determine (1) whether the regulation prohibits the use of misoprostol to induce abortion and (2) whether the regulation prohibits use of the drug methotrexate to treat ectopic pregnancies.

These questions stem from two tenuous claims raised by the plaintiffs in Cline. First, the plaintiff-abortion providers claim that the Oklahoma regulation prevents the use of misoprostol for chemical abortions because misoprostol's label does not include instructions for use in abortion; and if there are no instructions for abortion uses, it cannot be used for abortion under the Oklahoma regulation, resulting in a de facto ban on chemical abortion. But this claim ignores the clear wording of the regulation which points to the RU-486 label—a label that specifically requires use of misoprostol as the second drug in the regimen. Further, the FDA also references the use of misoprostol throughout all of its communications on the regimen as well as in the required patient agreement.

Further, the plaintiffs' claim ignores standard rules of statutory construction. Had the legislature intended to ban all chemical abortions, other aspects of the Oklahoma regulation would be make no sense, such as a requirement that women undergoing chemical abortion be examined by a physician before administration of the drugs.

Second, the plaintiff-abortion providers claim that the Oklahoma regulation prohibits off-label use of drugs to treat ectopic pregnancies. This claim ignores the fact that the definition of "abortion" in Oklahoma law specifically excludes treatment for ectopic pregnancy. The operative definition of abortion delineates it as "the use or prescription of any instrument, medicine, drug, or any other substance or device intentionally to terminate the pregnancy of a female known to be pregnant with an intention other than ... to remove an ectopic pregnancy." In addition, this definition includes an "intent" element, meaning that an action does not constitute "abortion" unless there is specific intent. That intent that is missing in the treatment of ectopic pregnancy.

For these reasons, the Oklahoma Supreme Court should answer "no" to both questions—the regulation does not prohibit the use of misoprostol for abortions as long as physicians are following the RU-486 label, and the law does not prohibit use of methotrexate for treatment of ectopic pregnancies because treatment of ectopic pregnancy is not "abortion."

It is unknown how the US Supreme Court will respond once the Oklahoma Supreme Court answers the certified questions now before it. The court could order further briefing, or it could conclude that full review is not necessary. But with increased action each year from state legislatures seeking to protect women from the harms of chemical abortion—seven states enacted regulations in 2013 alone—states need clear direction sooner rather than later. Cline is the first case before the court since 2007 that will test whether the court really meant what it said in Gonzales, and the facts and the law are on Oklahoma's side.

Mailee R. Smith is Staff Counsel for Americans United for Life, where she provides legislative consultation on the constitutionality of bills related to abortion, including informed consent, ultrasound requirements, abortion bans, fetal pain information, and Mifeprex (RU-486) regulation. Ms. Smith's legal expertise also extends to bioethics, such as bans or regulation of destructive embryo research, human cloning, and human egg harvesting.Ms. Smith is also AUL's primary litigation attorney, drafting amicus curiae briefs on behalf of AUL and its clients on a wide array of life issues. Ms. Smith received her law degree from Valparaiso University School of Law, where she graduated magna cum laude.

Suggested citation: Mailee R. Smith, Oklahoma's Restrictions on the Use of RU-486 Follow FDA Restrictions, JURIST - Sidebar, Oct. 16, 2013, http://jurist.org/sidebar/2013/10/mailee-smith-cline-ru486.php.

This article was prepared for publication by Alexandra Cabonor, an associate editor with JURIST's professional commentary service. Please direct any questions or comments to him at professionalcommentary@jurist.org

Opinions expressed in JURIST Commentary are the sole responsibility of the author and do not necessarily reflect the views of JURIST's editors, staff, donors or the University of Pittsburgh.

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