[Report by Jim Dickinson] Years of complaints about the adequacy of CDRH device labeling requirements are echoed in a new raft of complaints about the labeling of intrauterine devices (IUDs) implanted in an estimated 15 million American women. Most recent publicly available data show over 20,000 FDA-logged IUD adverse events a year, according to data compiled by the Institute of Safe Medication Practices (ISMP). But these understate actual postmarket adverse reactions, according to New York-based Inner U Diagnosed film director Kathryn Shasha, herself an injured IUD user.
According to ISMP’s Web site, IUD labeling when first approved by FDA disclosed to physicians 20 potential adverse reactions, but these were rarely relayed in full to women receiving the IUDs. Implanted women reported among themselves 32 additional adverse reactions. Eighteen more adverse reactions were subsequently reported by users in social media postings, the site says. Reported side effects not reflected in approved labeling include heart palpitations, hair loss, chronic fatigue, weight gain, blurred vision, broken teeth, skin rash, swollen feet, coordination difficulties, convulsions, temporary limb paralysis, suicidal thoughts, rage and psychiatric disorders. Most of the market-leading IUDs are regulated not by CDRH alone, but in consultation with CDER because they are combination products with hormone drugs. Drug-device combos usually give CDER the lead regulatory role. Shasha’s interactions with FDA over her concerns have been unsatisfactory, she tells FDA Webview. In June, 2019, she exchanged emails with a CDER pharmacist identified only as RL in an effort to get sufficient information to file an FOI request for postmarket experience reports on IUDs. RL, Shasha says, was “completely unhelpful.” On 11/29/19, she made a second effort with FDA’s Office of Women’s Health (OWH), which asked her to instead go to CDRH’s Division of Industry and Consumer Education. When Shasha explained that she wanted to “speak to someone about ensuring that women are being informed about IUD health risks and side effects,” Shasha says OWH did not respond despite 20 follow-up tweets. After this, Shasha gave up on FDA and focused her efforts instead on building a user network to warn women about the dangers of IUDs. One of her projects is a documentary film now in production on IUD issues. Like other device users who have had similar labeling-related and communication frustrations with CDRH, most notably concerning Bayer’s Essure contraceptive implant, dental amalgam and Lasik for vision correction, Shasha says patient informed consent should be required before IUD insertion. FDA ordered that requirement for Essure, but not for other IUDs. FDA seems to have tunnel vision on patient informed consent. Consult the agency’s Web site and search for “informed consent” and you will find statute-driven references only to clinical trial subjects, not patients receiving approved products. As a result, CDRH appears to have left IUD patient informed consent to the private sector, which Shasha finds worse than unhelpful. For example, she calls an IUD informed consent form for students and faculty at the University of California Berkeley “not only misleading but incredibly concerning. Giving information that pretends to inform patients of risks is almost worse than not informing them at all.” Her critique of that document can be found here. Asked to comment, FDA spokespersons and CDRH director Jeff Shuren did not do so. After deadline, the FDA Office of Media Affairs sent this response:
Intrauterine devices for contraception, also referred to as long-acting reversible contraception, that incorporate active substances (like copper or levonorgestrel) are regulated in the U.S. as drugs per 21 CFR 310.502(a)(8); however, they are usually co-packaged with an inserter that is required for placement, which is regulated as a device. When the intrauterine device and inserter are co-packaged together, they are regulated as a combination product per 21 CFR 3.2(e)(2). FDA bases approval decisions for IUDs on a benefit-risk assessment of the totality of the data presented in each marketing application. The specific reasons for a particular approval decision are included in the drug’s review summary available at Drugs@FDA https://www.accessdata.fda.gov/scripts/cder/daf/ (search by drug name, active ingredient, etc.).
Here is some information about approved birth control medications, including IUDs (note, these are types of contraceptives and birth control methods, not brands or specific products): https://www.fda.gov/ForConsumers/ByAudience/ForWomen/FreePublications/ucm313215.htm. More information is available here: https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/default.htm
Here is an FDA guidance on informed consent, which includes information for medical product sponsors: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/informed-consent
Here is information on labeling for IUDs: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=884.5360 and https://www.govinfo.gov/content/pkg/CFR-1996-title21-vol8/pdf/CFR-1996-title21-vol8-sec801-427.pdf, which includes the list of warnings and precautions.
This Web page has information on how the public should report adverse events to the FDA:
https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program
Also, this page on FDA’s website has general information on different types of birth control, including benefits and risks: https://www.fda.gov/consumers/free-publications-women/birth-control
