Addressing Many of the Myths the Media is Repeating about the FDA’s Approval and Management of Mifeprex (Mifepristone)

Part Two

By Randall K. O’Bannon, Ph.D., National Right to Life Director of Education & Research

Editor’s note. This is the second in a series by Dr. O’Bannon in which he debunks seven of the many, many myths about how and why the FDA approved and managed Mifepristone. On Monday he addressed Myths 1 & 2.

MYTH3: After going through the same rigorous testing and evaluative processes the agency requires of all other drugs, the FDA gave Mifeprex (mifepristone) its full and unqualified approval.

Reality:The FDA approved mifepristone under a special process that allowed for accelerated approval and more limited initial testing but enabled the agency to more closely monitor and control distribution in light of identified safety risks.

Much has been made of the FDA’s use of its special Subpart H designation to authorize “accelerated approval”for Mifeprex (mifepristone), a status reserved for “new drugs for serious or life-threatening illnesses.” Given that normal pregnancy is neither a “serious” nor “life-threatening illness,” this obviously represents a misapplication of the statute, merely reinforcing that the FDA had no business considering a drug to kill babies in the first place. 

This did enable the agency to cut some corners for the FDA’s consideration of the drug in terms of the number or depth of the studies required before the application was filed. But it is not clear that this ultimately gave mifepristone much of a time or procedural advantage; the drug’s sponsor still had to collect and present data from U.S. trials and took at least four years to get approval when the average approval time for other drugs was a year and a half.

Perhaps more importantly, use of the Subpart H status resulted in mifepristone’s approval coming with a strict set of distribution controls, many of which still existtoday in some form, much to the dismay of the abortion industry.

The data presented to the FDA showed a drug whose efficacy diminished the farther along the gestation and customarily came with a lot of serious cramping, bleeding, and other significant side effects, some significant enough to put women in the hospital or even threaten their lives. 

Acting upon that data, the FDA approved the drug but used its Subpart H authority to require further post-marketing data and to limit mifepristone’s distribution, requiring that these pills only be distributed through “certified” prescribers. Those prescribers (originally only doctors) had to sign agreements indicating they were familiar with mifepristone’s complex regimen and special risks, shared these with patients, screened patients for gestational age and ectopic pregnancy, and made sure patients knew where to find help in the event of an emergency.

This hampered rollout and still serves as a disincentive for many potential prescribers today who are not willing or are unable to comply with the certification requirements.

MYTH 4: Approval and modifications to the abortion pill protocol were supported by the best, most objective scientific studies.

RealityThe FDA relied too heavily on flawed studies and incomplete data from partisan abortion advocates and ignored strong scientific evidence to the contrary.

In the drug evaluation hearing and later in the published results of the U.S. trials, the abortion pill’s sponsors admitted that their “success” or efficacy rates in U.S. trials lagged behind that of their European counterparts. They attributed this, in part, to abortionists’ unfamiliarity with the drug and the amount of bleeding involved.

The FDA noted that efficacy dropped off with gestational age and limited use to women no more than 49 days past their last menstrual period (LMP), but in doing so accepted a 92% completion rate as sufficiently efficacious. 

Of course, sponsors promised to do better with more experience and new protocols and in due course, once the drug had been on the market for a few years, the abortion industry produced new studies claiming much higher rates (98-99%). These studies were offered not just as proof of greater efficacy, but as efforts to get the FDA to loosen its protocols, alter dosages, to extend the gestational cutoff, to reduce the number of required visits, to expand the pool of prescribers.

It appears to be a tactic that worked, with the FDA announcing exactly those changes in March of 2016 and citing such studies in its 3/29/16 Clinical Review recommending those changes.

Whether it was 1) inappropriately applying safety and efficacy standards commonly used for drugs given to ill or suffering patients in need of treatment to perfectly health patients where the drugs were meant to induce ill effects, or whether 2) the FDA had accepted the idea that dead babies and suffering but surviving mothers were the agency’s evaluative criteria, the agency, in taking these abortion industry studies at face value and making these concessions, ignored some serious methodological flaws and some serious data gaps.

Ignoring lost patients

Consider for example the study “Efficacy and safety of medical abortion using mifepristone and buccal misoprostol through 63 days” by Mary Gatter, Kelly Cleland, and Deborah L. Nucatola, from the April 2015 issue of Contraception, cited more than thirty times in the FDA’s 2016 official Clinical Review.

Gatter and her teamstudied the records from 15,980 patients who had chemical abortions at Planned Parenthood between April of 2006 and May of 2011. Among the 13,373 who completed the regimen and returned for follow-up, researchers reported an efficacy rate of 97.7% with rates of infection and transfusion at less than a tenth of a percent.

Discerning readers will note that data from 2,470 patients are missing from the analysis.

Regarding this, the FDA’s Clinical Review notes the high percentage (15.5%) of patients in Gatter’s study lost to follow up, says that “Follow-up after taking Mifeprex and misoprostol is necessary,” but simply allows that this sometimes happens in studies.

While the FDA must work with the data it has, it simply cannot ignore the implications of a data gap like this, particularly given what it knows about this drug and what it should know about the abortion industry and its clients.

Some patients with problems may return to the clinic where they got their pills, but others, particularly if they are having problems, may be much more likely to visit their own doctor or the local emergency room.

If those patients are the ones having most of the complications and the failed or incomplete abortions, not only might the safety and efficacy reports from industry studies be wildly off, but ignoring this data could make an unnecessary, avoidable health crisis more likely.

This is not mere speculation. Studies that rely on emergency room data, rather than the reports of abortion advocates or clinic staff of just those women who return to the clinic or respond to clinic phone calls, obtain much different safety and efficacy data.

Complications show up in the emergency room

A 2015 study of emergency room visits by University of California, San Francisco researcher Ushma Upadhyay (“Incidence of emergency department visits and complications after abortion,” Obstetrics & Gynecology January 2015) found more than one in twenty (5.19%) chemical abortion patients reporting a complication of some sort.

(Upadhyay maintains that most of these complications were minor, but this ignores the fact that for the women involved here, they were serious enough to merit a trip to the ER).

Simply accepting and repeating official safety and efficacy figures isn’t good enough. When the British government was reporting just one single complication among 23,061 chemical abortions performed between April and June of 2020 (The New Statesman, 12/15/20), a former executive and public health researcher with family planning giant Marie Stopes International did his own direct survey of the National Health Service’s Trusts (which manage the country’s acute hospital services and emergency care) and obtained much different results.

Kevin Duffy of Percuity found that 5.9% of chemical abortion patients were treated during that time for complications connected to incomplete abortions or “retained products of conception.”  Three percent of women there required surgery to deal with incomplete abortions and 2.3% of these patients were treated in Trust hospitals for hemorrhage (Percuity, 10/27/21, at 

Where the government identified just one patient reporting a complication, Kevin Duffy of Percuity found more than a thousand by contacting the hospitals directly.

Relying on studies performed under other conditions

The FDA’s most recent changes to the protocol were justified, at least in part, by appeals to studies that did not really establish the safety of those changes. 

For example, the most recent FDA “Summary Review” looking at revisions to protocol spelled out in the agency’s special Risk Evaluation and Mitigation Strategies (REMS) for mifepristone (FDA 1/3/23, at appeals to a study by long time abortion activist Daniel Grossman and several colleagues “Mail-order pharmacy dispensing of mifepristone for medication abortion after in-person clinical assessment” that appeared in the March 2022 issue of Contraception.

Offered in support of a change that involved dropping requirement that the patient visit the prescriber in person to pick up their pills, the study actually did little to establish that this visit was medically unnecessary, since all patients involved in the study were still screened in person and gestational ages were still determined by an in-person ultrasound or a physical examination.

The only difference was that they were able to pick up their pills at the pharmacy rather than the prescriber’s office. 

While this might theoretically show, at most, that pills picked up at the pharmacy worked as well as those picked up at the office, what it does not show is that the in-person screening for gestational age, ectopic pregnancy is unnecessary and can be done away with or that it can be done just as well by a phone call or a video interview. This is not something the study examined. 

There are no grounds from the study to conclude that women who do not have in-person ultrasounds or undergo physical examinations fare as well as those who did receive such in-person screening.

The FDA’s commitment to scientific objectivity, to public health, to patient health and safety must mean something more than uncritically accepting deficient data and claims or flawed, biased studies and simply taking the word of researchers who are trying to help the industry find more prescribers and sell more product.

Ignoring inconvenient truths

Perhaps it was a matter of timing or access, but notably the FDA ignored a Canadian study of 39,856 patients that appeared in the January 3, 2023 online edition of the Annals of Internal Medicine by Ning Liu and Joel G. Ray, two researchers from the University of Toronto. What was interesting about this study was that it already used a system in some wayssimilar to that now being authorized in the U.S., allowing women to obtain their prescriptions from regular medical personnel but actually having them pick up mifepristone at pharmacies.

The results show that this is not nearly as safe or benign as the FDA and the mifepristone lobby would have us believe. Under that protocol, emergency room visits jumped to 10.3% — at least one out of every ten patients.

There is no reasonable way that a drug with this profile can be considered safe, no way that data like this could be grounds for loosening controls on distribution.

Arguments that this study came out too late for FDA consideration ring hollow. The Grossman study mentioned above had not yet been published when the FDA used it to justify its latest REMS modifications, but the FDA had a close enough relationship with Grossman to know of and obtain a copy of his study before it actually went to press. While the FDA clearly had a close relationship with members of the American abortion establishment, they appear to have lacked any similar relationship or access with the Canadian team.

Clearly, the FDA needs to critically and objectively assess all relevant data bearing on its drug decisions rather than cherry picking only that data and those studies that support the industry’s — or administration’s — public policy agenda.