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Expect a considerable amount of attention to be focused on the results of a pending government-funded study of the efficacy of over-the-counter (OTC) spermicides, for these findings will lead regulatory officials in determining the fate of a small, but important, segment of the contraceptive market.
While no one questions that OTC spermicides do reduce the risk of pregnancy, exactly how much has yet to be determined, says James Trussell, PhD, associate dean of the Woodrow Wilson School of Public and International Affairs and director of the Office of Population Research at Princeton (NJ) University. Much of the existing information on OTC spermicides is outdated, with some trials conducted more than 30 years ago.
If all spermicide products have to submit efficacy data, though, the subsequent costs would lower profits in what represents a small segment of the contraceptive market. This dollar loss might halt production and, in turn, take away a woman-controlled birth control option, asserts the Washington, DC-based Association of Reproductive Health Professionals (ARHP).
"Actual-use clinical trials would not only be extremely difficult to design, but would potentially turn a low-profit product into a no-profit product, thereby encouraging manufacturers to cease production of spermicides altogether," reads a portion of an ARHP statement presented at a Food and Drug Administration joint committee meeting on the subject. "They will severely limit the availability of safe, affordable, effective birth control options for women, reduce the control women have over managing their own health, and will lead to unintended pregnancies as well as the potential acquisition of STDs."
Members of the four FDA advisory committees were clear in their request for more efficacy information on OTC spermicidal products. The committees convened in a joint session in response to the FDA’s posting of a Notice of Proposed Rulemaking,1 which calls for a more rigorous examination of such products. If the FDA elects to implement the proposed rule, manufacturers of currently marketed spermicides would have to conduct clinical trials to establish the efficacy of their products.
(Editor’s note: While FDA advisory committee members concluded that currently available OTC spermicides could be said to help reduce risk of chlamydia and gonorrhea transmission, they were less clear on whether these products were safe to use long-term. Contraceptive Technology Update will examine this action in an upcoming issue.)
While OTC spermicides may not be the first choice of birth control for most women, they are easily available, don’t require a doctor’s prescription, and are user-controlled. These products employ a carrier, such as foam, cream, gel, suppository, or film, to deliver nonoxynol-9 (N9) to destroy sperm cells. (Use the patient handout included in this issue to counsel patients on the use of vaginal foam.)
Such vaginal chemical contraceptives have been in use in the United States for more than 40 years, with their use "grandfathered" into FDA regulations under the monograph process. However, when this class of drug was recently reviewed by the FDA, officials determined that the effectiveness of N9 cannot be considered separately from its carrier. A strict interpretation of this ruling, if enacted, would force existing OTC spermicide manufacturers to file new drug applications and submit clinical efficacy data to receive FDA approval.
No one is questioning that spermicides reduce the risk of pregnancy, says Trussell, who presented information on spermicides’ contraceptive efficacy at the joint meeting. But none knows by how much, he points out, since not one of the clinical trials conducted on the subject meet modern standards of design, execution, analysis, and reporting.
According to an analysis of 34 studies,2 20 of the studies are more than 30 years old and do not lend themselves to definitive comparison with other contraceptive methods.
"How effective are different spermicides during perfect use?" Trussell asks. "Do spermicides reduce the risk of pregnancy? Definitely yes. By how much? Who knows? There are far too many questions with no answers."
That’s why the Bethesda, MD-based National Institute of Child Health and Human Develop-ment (NICHD) has issued a request for proposals for an efficacy trial of spermicidal agents, says Joanne Luoto, MD, MPH, who also presented at the joint meeting.
"The FDA is looking more carefully at all the evidence, and because of the absence of previous clinical trials, we don’t have enough evidence now to evaluate the role of dosages that may vary three- or fourfold, or the interaction with the actual carrier," she says.
The NICHD study grant, when it is awarded, will include up to four spermicides, with a three-phase clinical trial to determine their contraceptive safety and efficacy. Dennis J. Barbour, JD, ARHP president, says he hopes the FDA will wait to implement any changes until after the NICHD data are received.
"One of the major fears that we have is that perhaps unnecessarily subjecting the spermicides to an NDA process or something similar to it would cause confusion on part of the public and would cause them to stop using them," he notes. "And we have enough of that problem in this field already as it is."
The onus now is on the FDA to come out with a proposal for how to proceed in the matter, says Lisa Rarick, MD, director of the FDA’s division of reproductive and urologic drug products.
"We have to figure out a time frame as to when [efficacy] information would be needed, and also figure out a way to deal with the concept that this is a small population of users, a very small market," Rarick notes. "Let’s say the first trial gets done, and the gel is no different than a foam, how far do we need to push sponsors to get specific final formulation information? I think there has to be some flexibility in getting this information and being able to look at it."
The problem is that studies take a long time, she continues. "If you don’t tell everybody they have to do this for each final formulation now, it’s going to be five or six years before you know from any one of these trials that they’re either the same or that they’re different," Rarick says.
And then what do you do? "If they are different, then do you say everyone has to do final formulation studies and wait another five years?" Rarick asks. "I don’t think the answer was clear about what the agency itself should do, but I think the committee was clear that the effectiveness information needed to be gathered."
1. Food and Drug Administration. Vaginal contraceptive drug products for over-the-counter human use. Notice of proposed rulemaking. 60 Fed Reg (Feb. 3, 1995) 6,892-6,903.
2. Trussell J. "Contraceptive Efficacy of Barrier Contraceptives." In Mauck CK, et al (eds). Barrier Contraceptives: Current Status and Future Prospects. New York City: Wiley-Liss; 1994.