[Docket No. FDA-2019-N-3722]
Thank you for the opportunity to speak on the Agile transdermal contraceptive patch AG200-15. Being able to space, plan, and prevent pregnancy is vital to women’s health. We appreciate the agency’s interest in fostering the development of a wide range of innovative, safe and effective methods that prevent pregnancy regardless of a person’s age, race, ethnicity, body mass, or where they live.
My name is Sarah Christopherson and I am the Policy Advocacy Director at the National Women’s Health Network, a nonprofit advocacy organization that works to improve the health of all women. We are supported by our members and do not accept financial support from drug companies or medical device manufacturers. We bring the voices, concerns and needs of women consumers to policy and regulatory tables. Since the NWHN’s founding more than 40 years ago, we have brought the voices of women to the FDA, advocating for medical products that meet women’s real needs and a drug development process that reflects women's lived experiences.
My purpose today is to encourage this panel to consider the questions here differently than they have been presented by FDA staff in the briefing document, in several key ways:
I. Filling an unmet need
We know from speaking to women that there is a demand for safe, user-controlled methods that don’t have to be taken daily, taken orally, or inserted into the vagina. The briefing document repeatedly side-steps the question of whether this is an unmet need—in the plain meaning of that phrase—by lumping all combined hormonal contraceptives together, regardless of their route of administration, and by narrowly defining “unmet need.” But we know that a daily pill isn’t the same user experience as a weekly patch, and that contraceptive users benefit from having access to a full range of methods. In fact, the data presented in the briefing document itself make that clear.
In arguing against the Applicant’s claim that dosing convenience could increase user compliance, the briefing document relies upon a study of contraceptive users that extrapolates compliance from acquisition data. Based on this study, the briefing document concludes that “switching to a transdermal system or ring did not improve refill patterns as greater proportions of women on these products were delayed refillers.”
But a deeper dive into the study finds that, “Among delayed [OC] refillers, the mean percentage of timely refills increased from 47.9% while on OCs to 72.2% while on the patch.”
That strongly suggests that while the patch isn’t the right option for everyone, there is a subset of contraceptive users who want—and would benefit from—access to a lower-dose patch.
Furthermore, in the appendix in Section VIII, the briefing document makes a strong, albeit unintentional, argument for considering AG200-15 as filling an unmet need. The document notes that “drospirenone-containing COCs and the [lone, existing] transdermal system had the largest decreases in utilization” between 2006 and 2018—a period that we know corresponds to increased public concerns about those methods’ safety. That decrease in use, combined with earlier data showing that compliance significantly improved for a subset of patch users, suggests that safety concerns, not a lack of interest, are driving consumers away from the patch.
Thus the central question for the committee shouldn’t be whether the new patch is safer than all other approved estrogen-containing CHCs but whether it’s safer than the only other patch currently on the market. If, in fact, AG200-15 is as safe as other non-patch CHCs—which the briefing document seems to suggest—then it represents a significant improvement over what’s currently available to women.
II. Efficacy matters but it’s not users’ only consideration
Human sexuality, and even pregnancy intention, can be complicated, and while a method’s effectiveness is important, it doesn’t capture the full range of trade-offs that people make in choosing the contraceptive option that’s best for them. When women are given the chance to make non-directive, fully informed decisions for themselves with access to a full range of methods, they are much more likely to be satisfied and much more likely to continue a method. In contrast, studies have found that when users feel pushed into a method that’s not right for them, many “rapidly discontinue” those methods.
In short, a nominally less effective method you like and stick with is ultimately much more effective than a nominally more effective method you don’t like and discontinue. Instead of creating an arbitrary cut-off for Pearl Indices, we encourage the panel to balance efficacy against other considerations, such as expanding the number of options available to women.
We also question whether the FDA has adequately grappled with the impact of diverse populations on efficacy data. The briefing document acknowledges the limitations in comparing data collected in recent, more diverse phase 3 trials to earlier trials but ultimately doubles down on the idea of a historical “upper bound.” But a product tested in a truly representative group of potential users is likely to have a higher PI than a previously approved product tested primarily or exclusively in thin, white women. As the Applicant notes, those effects compound the closer the trial group gets to representing real-world users.
The NWHN has a long history of working with the agency to address the low rates of participation by diverse populations to allow for analysis and proper labeling of approved medical devices and pharmaceuticals. This September, we commended the FDA for releasing guidance that explicitly encouraged contraceptive trials with diverse groups of women, including women of color, adolescent women, women older than 35, and women with high body mass indices. If the agency is serious about testing products in representative groups going forward, it needs a much better understanding of how those PIs compare to PIs of less broadly tested products.
Finally, the briefing document affirms the FDA’s commitment to contraceptive innovation and outlines “Contraceptive Products currently marketed in the US” as evidence of that commitment. But the list notably excludes one contraceptive method that has gained the FDA’s imprimatur: Natural Cycles, the smartphone contraceptive app cleared by the FDA last year.
While everyone here today understands the difference between this rigorous approval process and the expedited clearance given to Natural Cycles, the average contraceptive user just knows that the FDA gave its blessing to a smartphone app that has marketed itself as being “as effective as the Pill.”
But while Natural Cycles could have remained accessible to American women without the FDA’s blessing—just as its dozen or so un-cleared competitors can be downloaded and used right now—denying approval of AG200-15 on efficacy grounds serve to keeps a far more effective contraceptive product off of the market while a less effective one touts its FDA bona fides. And while Natural Cycles is only as effective as its users’ ability to follow a strict daily regimen on their own without clinical support, AG200-15’s limitations can be highlighted prominently on the label and explained in contraceptive counseling appointments by trained clinicians.
In conclusion, we encourage the panel to recommend approving AG200-15 with a strong label that gives women the full information they need to make smart decisions for their reproductive health.
Thank you for your consideration.