Officials from the US Food and Drug Administration’s (FDA) Center for Devices and Radiological Health (CDRH) took to the New England Journal of Medicine on Thursday to explain the wide array of clinical trial designs and data sources that may be used to support the safety and effectiveness of medical devices.
Unlike for pharmaceuticals, which generally see double-blind, randomized, Phase 3 trials assessing outcomes prior to approval, "practical limitations related to the device or disease condition require alternative approaches" for many devices, CDRH’s Owen Faris and Jeffrey Shuren write.
For example, they say it may be infeasible to conduct a blinded trial of an implantable device because it would be unethical and impractical to implant a placebo device. And for some devices, alternative data sources, such as existing registries or modeling techniques, can allow regulators "to have a good idea of the risks and benefits of the device without the need for conducting detailed trials," they say.
For the majority of devices, the benefits and risks can be revealed through registries and evolve as clinical techniques are refined and the technologies are modified and improved.
"Such a continuous improvement cycle would be impossible if every device iteration required a full trial to test its safety and efficacy," Faris and Shuren add, noting that FDA has in many cases accepted a somewhat greater degree of uncertainty regarding those benefits and risks early in a device's life cycle.
FDA entered the device clinical trials arena after several deaths and claims by about 200,000 women that they were harmed by the use of the Dalkon Shield, an intrauterine device (IUD) intended for contraception.
Congress responded by passing the Medical Device Amendments to the Food, Drug, and Cosmetic Act in 1976, adding requirements that a device must meet to be lawfully marketed depending on its risk classification.
Most low-risk devices (e.g., prescription eyeglasses, elastic bandages and dental floss) are exempt from FDA review before marketing, although manufacturers are still subject to certain requirements.
Most moderate-risk devices (e.g., condoms, nebulizers and blood glucose meters) generally need to show that they are substantially equivalent to another device already cleared by FDA, with the authors noting, "in most cases, this is achieved through bench (nonclinical laboratory) testing and without clinical data."
Higher-risk and more innovative moderate-risk devices (about 4% of all devices, according to the authors), generally require clinical evidence to show that the benefits of a technology outweigh its risks.
In addition to highlighting examples of high-risk devices and the trials conducted, the viewpoint notes FDA’s "breakthrough" or expedited access pathway, which recognizes that for some new technologies looking to address unmet medical needs, "it may be appropriate to accept a greater degree of uncertainty in order to expedite the availability of the device for patients, relying on postmarketing data to provide greater certainty about the safety or effectiveness of a device."
While pointing to a 2012 CDRH report on strengthening the National Medical Device Surveillance System, Faris and Shuren further note that patient perspectives moving forward will help to inform device trials and that partnerships at national and international levels "are needed to ensure that appropriate data collection continues throughout the life cycle of a medical device."