New labeling for the Pill: Will it change how you prescribe oral contraceptives?

Guidance now under review may not reflect most current information 

When it comes to using combined oral contraceptives (OCs), clinicians and patients look to drug package labeling for the most current information on how the Pill may be safely and effectively used.

If new industry guidance for package labeling goes into effect, however, combined OC labels may not reflect the most current thinking in contraceptive provision. While the guidance offers a more simplified approach to the label and patient instructions, several women’s health groups have called for the directive to contain more updated medical information, a more thorough explanation about contraceptive method failure rates, and expanded information on the noncontraceptive benefits of the Pill.

"My understanding is that package labeling is intended to provide accurate and up-to-date drug information for consumers and providers," says David Grimes, MD, vice president of biomedical affairs at Family Health International in Research Triangle Park, NC. "The proposed labeling I reviewed was neither accurate nor up to date."

Groups such as the American College of Obstetricians and Gynecologists (ACOG), National Association of Nurse Practitioners in Women’s Health (NPWH), both based in Washington, DC; Planned Parenthood Federation of America (PPFA) in New York City; and drug manufacturers such as Raritan, NJ-based Ortho-McNeil Pharmaceutical and Philadelphia-based Wyeth Pharmaceuticals, have filed comments with the regulatory agency. The deadline for filing comments was May 4, 2004. The FDA is analyzing the comments, says Susan Cruzan, FDA spokeswoman.

Kirsten Moore, president of the Washington, DC-based Reproductive Health Technologies Project, says, "Our concern is that the current draft label falls short of the clinical literature and represents a step back in time — overstating the health risks associated with oral contraceptive pill use and underestimating some of the benefits. While that may just be the work of cautious officials, the more conservative approach gives some of us cause to worry that information about birth control may be the latest victim in the abuse and misuse of science to fit a politically motivated, ideologically driven agenda."

Review the history 

The guidance now under review includes wording for health care provider labeling and patient instructions that manufacturers will use for new drug applications and abbreviated new drug applications. The FDA issued a first guidance for comment in June 2000; the one now under review includes changes from the original draft. (To review the current draft guidance, go to the FDA web site, www.fda.gov. Under "Products FDA Regulate," click on "Drugs" under "Quick Info Links," click on "Guidances" then scroll down to "Labeling (Draft)." You may view the draft guidance, "Labeling for Combined Oral Contraceptives.")

The 2000 rendition of the guidance was "much better," says Susan Wysocki, RNC, NP, NPWH president and chief executive officer.

"We provided comments about the new labeling," says Wysocki. "There were a number of issues that seemed to be backward slides."

One concern shared by ACOG, NPWH, and PPFA is the draft guidance’s call for combined pill users to have an annual examination and laboratory tests. The guidance currently states, "Women who are using oral contraceptives should have an annual history and physical examination, including special reference to blood pressure, breasts, abdomen, and pelvic organs, as well as cervical cytology and relevant laboratory tests."1

Medical opinion has shifted from requiring breast and pelvic examinations prior to initiation of hormonal contraception to encouraging exams as part of routine care. A 2001 review of existing recommendations for hormonal contraceptives found that in most cases, waiting to schedule such exams prior to prescribing represents an unnecessary and potentially dangerous delay.2

"Indeed, the United States Agency for International Development, the World Health Organization, the International Planned Parenthood Federation, the American College of Obstetricians and Gynecologists, the Society of Obstetricians and Gynaecologists of Canada, the Royal College of Obstetricians and Gynaecologists, and the American Academy of Pediatrics all conclude that pelvic examinations are not necessary prior to the initiation of OCs, even among adolescents," stated PPFA’s written comments to the FDA.3

Where are the benefits? 

Family planning clinicians regularly include discussion of the noncontraceptive benefits of the Pill, such as protection against endometrial and ovarian cancers, when discussing birth control choices. The noncontraceptive benefits section of the draft guidance lists only menstrual-related benefits, says Wysocki.

The current draft omits additional health benefits published in previous guidance and supported by current medical literature such as decreased incidence of ovarian cysts, ectopic pregnancy, endometrial cancer, ovarian cancer, and benign breast tumors, stated RHTP’s written comments to the FDA.4 Research has shown that educating patients on the benefits of OCs increases compliance rates, the comments noted.4

"The proposed labeling lacks balance," observes Grimes. "It provides a listing of putative health risks, yet largely ignores the well-documented health benefits known for decades, including powerful protection against two cancers."

How to teach about use?

When counseling women on "will the Pill work?" clinicians include a discussion on typical and perfect use failure rates to help women understand the efficacy of the method. The probability table, a standard inclusion in Contraceptive Technology and current manufacturers’ combined OC labels,5 has been modified in the draft guidance and does not include perfect use information.

"This simplification overestimates the effectiveness of typical use of combined OCs and underestimates the effectiveness of condom use in preventing pregnancy," stated ACOG’s written comments to the FDA.6

By including perfect-use data, clinicians can help women increase their compliance with their chosen method by motivating them to achieve maximum protection against unintended pregnancy, stated PPFA’s written comments to the FDA.

The literature cited in support of the proposed labeling is obsolete, says Grimes. Important recent articles were missing, as were comprehensive reviews by organizations such as the Geneva-based World Health Organization (WHO). One such document is the WHO’s recently revised Medical Eligibility Criteria for Contraceptive Use.

Reinforcing providers’ instructions through pill packaging inserts helps women use OCs more consistently — if women understand the instructions. A study of Western European women showed that women who read and understood the information in pill packaging inserts were least likely to miss one or more pills per pack.7 Among those who understood little or none of the insert information, about 30% missed one or more pills per pack.

"Each year, thousands of health care providers prescribe millions of cycles of combined OCs to millions of women in the United States," added NPWH’s comments to the FDA. "It is imperative that the package insert and patient labeling that accompanies each cycle of combined OCs be complete, accurate, and clear; only then will providers be able to make sound medical recommendations and women be provided with the tools necessary to make informed decisions."8

References 

1. U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research. Guidance for Industry. Labeling for Combined Oral Contraceptives. Draft Guidance. March 2004. Accessed at: www.fda.gov/cder/guidance/5197dft.doc.

2. Stewart FH, Harper CC, Ellertson CE, et al. Clinical breast and pelvic examination requirements for hormonal contraception. JAMA 2001; 285:2,232-2,239.

3. Cullins V. Re: Docket number 200D-1350, "Draft Guidance for Industry on Labeling for Combined Oral Contraceptives" [letter]. Accessed at: www.fda.gov/ohrms/dockets/dailys/04/may04/050504/00d-1350-c00019-vol6.pdf.

4. Moore K. Re: Docket No. 2000D-1350 in the Federal Register 5 March 2004 (Volume 69) [letter]. Accessed at: www.fda.gov/ohrms/dockets/dailys/04/may04/050404/00d-1350-c00015-vol6.pdf.

5. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology. Bridging the Gap; 2004 [in press].

6. Hale RW. Re: "Draft Labeling for Industry on Labeling for Combined Oral Contraceptives; Availability" (Docket No. 2OOOD-1350. Accessed at: www.fda.gov/ohrms/dockets/dailys/04/may04/051104/00d-1350-c00021-vol6.pdf.

7. Rosenberg MJ, Waugh MS, Meehan TE. Use and misuse of oral contraceptives: Risk indicators for poor pill taking and discontinuation. Contraception 1995; 51:283-288.

8. Wysocki S. Re: Docket No. 2000D-1350 in the Federal Register 5 March 2004 (Volume 69) [letter]. Accessed at: www.fda.gov/ohrms/dockets/dailys/04/may04/051104/00d-1350-c00022-vol6.pdf.