FDA seems skeptical of push for birth control pill without a prescription

The Food and Drug Administration on Tuesday raised substantial concerns about a drugmaker's application for sales of a birth control pill without a prescription. 

A committee of independent experts who advise the FDA is meeting Tuesday and Wednesday to make a recommendation on whether data submitted by HRA Pharma is sufficient to allow over-the-counter sales of Opill, the company's contraceptive.

The FDA is not obligated to follow the advice of its outside experts, but their recommendations play an important role in the agency's decisions. 

Opill, generically known as norgestrel, could become the first over-the-counter birth control pill in the U.S. since oral contraceptives first entered the U.S. market more than 60 years ago.

HRA Pharma expects an FDA decision on the request in the summer, according to a spokesperson for the Paris-based drugmaker, which is owned by the consumer health-care company Perrigo.

Medical associations such as the American College of Obstetricians and Gynecologists for years have supported over-the-counter access to birth control without age restrictions.

HRA Pharma originally asked the FDA to approve sales of norgestrel in July, just two weeks after the Supreme Court overturned its own ruling in the case known as Roe v. Wade.

The Supreme Court's decision meant there was no longer a right to abortion under the U.S. Constitution. That triggered a series of legal restrictions on abortion in a number of states and also led to calls for expanded access to contraceptives and to medication that can end a pregnancy.

However, FDA staff have raised concerns that some consumers who should not take norgestrel — or who need to consult their doctor first due to health conditions — did not understand the drug label warning in a study, according to an agency briefing document publicly released Friday.

The FDA staff also said one-third of participants reported taking more norgestrel tablets than were actually dispensed in the study, a problem the agency called "improbable dosing." 

The underlying reasons for these errors are unclear but raise substantial questions about the accuracy of the study's results, according to the FDA.

"I just wanted to note that this finding of improbable dosing in this study is really quite extraordinary," Dr. Theresa Michele, who heads the FDA office of nonprescription drugs, told the advisory committee Tuesday. 

"In order for us to pick up on the fact that consumers were reporting doses that they didn't take," Michele said, "they had to way over-report to the point where they were reporting dosing beyond the number of tablets that they received." She said this raises concerns about whether other data was flawed but the FDA simply didn't pick up on it. 

The concerns by FDA staff also centered on whether consumers will understand norgestrel's warning label that women with breast cancer should not take the pill and women with vaginal bleeding should consult a doctor first. 

Women with a history of breast cancer are not supposed to take norgestrel because the medication contains progestin, which can increase the risk that tumors will recur.

HRA Pharma, in its own briefing document released last week, said 97% of 206 participants in a study who had a history of breast cancer understood the drug's label and chose not to use the pill. Six participants incorrectly chose to use norgestrel despite their cancer history, the company said.

But the FDA said only 5% of participants had limited literacy, so it's unclear if the study results would hold up in the general population. 

Dr. Pamela Goodwin, an oncologist, said the majority of women diagnosed with breast cancer are older than 50, which is generally considered to be past reproductive age by physicians.

About 25% of women diagnosed with breast cancer are under the age of 50, and about 40% of women in that group want to use contraception, said Goodwin, who presented for HRA Pharma.

About three-quarters of this population are using IUDs, or intrauterine devices, which means about 2.5% of breast cancer patients might be interested in using norgestrel, said Goodwin, a professor of medicine at the University of Toronto.

Women who have experienced unexplained bleeding between menstrual cycles are supposed to consult with their doctor before taking norgestrel, according to the drug's label.

HRA Pharma said 22 women in the study reported unexplained vaginal bleeding that they had not discussed with a doctor when they enrolled. Seven of these individuals chose to take norgestrel during the study. One of these participants spoke to a doctor during the study, while six did not.

The company said these six individuals did not consult a doctor because their bleeding was not frequent or they considered it to be normal.

A panel of doctors viewed norgestrel as appropriate for these women, HRA Pharma said.

Dr. Anna Glasier, an expert on reproductive medicine, told the FDA advisors that abnormal vaginal bleeding is a very common condition. Most women do not consult a doctor about the issue because these episodes typically resolve spontaneously, said Glasier, who presented on behalf of HRA Pharma.

Glasier said women should not be held hostage by having to see a doctor to get a safe and effective form of contraception.

The FDA also has raised concerns that norgestrel may not be as effective in the current U.S. population as the medication was when it was approved decades ago due to increasing rates of obesity, as well as lower adherence to a dosing regimen that requires taking the pill at the same time each day.

These factors could affect norgestrel's effectiveness at preventing pregnancy in a nonprescription setting, according to the FDA.

FDA staff in their briefing document last week said they are not aware of any data from the past two decades on the effectiveness of the drug.

Glasier said it is true that clinical trials that led to the approval of progestin-only birth control pills such as norgestrel were conducted at a time when study standards were not as rigorous as today.

But Glasier said contraceptives such as norgestrel have been used by millions of women over decades and have stood the test of time. She said it would be clear by now if these birth control pills were not effective at preventing pregnancy.

HRA Pharma's briefing document said the failure rate of progestin pills such as norgestrel is low.

An estimated 7% of women who use such contraceptives will have an unintended pregnancy in the first year, according to the document.

That is about the same failure rate as the other type of birth control that contains both progestin and estrogen.