[FDA Docket No. FDA-2016-N-1149]
The National Women’s Health Network is 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 insurance companies, drug companies, or medical device manufacturers. Since the NWHN’s founding 40 years ago, we have brought the voices of women to the FDA, advocating for medical products that meet women’s real life needs and a drug and medical device development process that reflects women's lived experiences.
We appreciate the FDA’s continued commitment to monitoring drug and device safety and efficacy and acknowledgment of the importance of off-label use and communication for patient and consumer health. We respectfully submit the following comments on “Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products,” and we look forward to working with the FDA to ensure that patient and consumer safety continue to be placed in the highest regard.
FDA defines off-label use of drugs as “use for indication, dosage form, dose regimen, population or other use parameter not mentioned in the approved labeling,” and currently prohibits off-label promotion of drugs and medical devices. Off-label communication may mean many things, including manufacturer-physician communication, direct-to-consumer (DTC) advertisements, peer-reviewed journal articles, etc. All of these forms of communication impact the care that patients receive, even if subtly or unconsciously. This is significant because, as the FDA itself notes, “approval of a drug or medical device for one intended use does not assure its safety and effectiveness for other uses.”
The current regulatory framework already provides significant flexibility, and allows doctors and health care providers to prescribe drugs and devices off label and exchange information. In fact, it is already common medical practice for health care providers to do so. Additional uses and benefits of a drug or medical device may only become evident after the drug’s approval, and in some cases, it makes sense for providers to prescribe to patients off label; e.g. when evidence-based research shows a different dose or timing of a drug is more effective or safer than the FDA approved regimen. When used appropriately, off-label use can provide evidence-based treatment to patients regardless of the original indication.
We recognize that communications of unapproved use information can have real benefits for individuals and the public. In very specific circumstances, it can actually promote health and health care access. For example, before mifepristone (medication abortion) received an updated, evidence-based label in March, health care providers had used an evidence-based dose that differed from the original approved use. Providers were also able to prescribe mifepristone to women beyond the then-approved 7 weeks (in states where this was not expressly prohibited). In these cases, off-label use, and the communication among providers about the off-label use, improved women’s health. However, drug and device sponsors should not be able to market their products off label when adequate safety and efficacy studies were not conducted on those uses.
Off-label promotion of menopause hormone therapy (HT) persuaded women and prescribers that the drugs reduced the risk of cardiovascular disease, and could possibly reduce the risk Alzheimer's without well designed long-term clinical trials to back up these claims. Off-label promotion included DTC ads, both branded and unbranded, celebrity endorsements, articles in scientific journals that had been “ghostwritten”, pre-made slide sets for researchers, and influence in shaping the content of Continuing Medical Education (CME) courses. As a result of these off-label communication tactics, hundreds of thousands of women developed breast cancer. Off-label promotion is not solely a matter of ethics or good marketing practices - the consequences have real-world impact, including disability and death for the women affected.
Some drug and device makers have argued that off-label communications are free speech, and that restricting those communications—as long as they are “truthful and non-misleading”—violates the First Amendment. The right to free speech ensures that members of the public are able to freely discuss their personal experiences on forums like drug informational sites, chat rooms, and so on. But when a drug or device sponsor communicates to the public, there is a heightened level of responsibility. These “First Amendment defenses” should be viewed in the context of a larger, cross-industry effort to undermine regulatory public health, safety, and environmental protections, and they should be rejected as such. Drug and device manufacturers should not be allowed to hide behind the First Amendment in order to market their products in ways that undermine the integrity of the FDA’s regulatory role and review process.
We believe that with the right information, women can and do make the health care decisions that are right for them. But this depends on women having the scientific evidence about safety and efficacy gained through clinical trials, which are circumvented when a manufacturer can turn to off-label communications. Without these trials, women are left to play guesswork when it comes to their health and how a drug or medical device will act in their body.
We have spoken at length about the need for women, people of color, and other sub-populations to have clinical trials that represent them. Drugs and medical devices react differently in different communities; allowing drug and device sponsors to communicate about their products both to providers and patients eliminates the incentive to conduct clinical trials and nullifies the FDA review process. These groups especially rely on the FDA to ensure that drugs and devices are tested in populations like them; allowing sponsors to bypass this process harms the very populations that are already most vulnerable to being excluded from clinical trials.
In closing, we implore the FDA to reject these attempts to undermine the drug and device regulatory process that protects public health and the American public. We have worked too hard and come too far to retreat to the days when people could easily be fooled by manufacturers’ marketing gimmicks.
We hope you will take our testimony into account as you consider whether to undertake new rule making or guidance affecting the safety, efficacy, and patient and provider understanding of these drugs and devices.