FDA Finalizes Weight-Loss Device Guidance Setting Minimum Weight-Loss Margins by Claim

The US Food and Drug Administration has finalized guidance on how makers of weight-loss devices should design their bench testing and clinical studies, setting out the minimum amount of weight loss the agency expects to see for each type of weight-related claim, according to the FDA's guidance page and the final guidance document, which is dated March 13.

The guidance, "Medical Devices with Indications Associated with Weight Loss - Premarket Considerations," was issued by the Center for Devices and Radiological Health. It applies to premarket approval applications, investigational device exemptions, 510(k) notifications and De Novo requests for devices with indications such as weight loss, weight reduction, weight management or obesity treatment.

Regulatory Focus, published by RAPS, reported on March 12 that the document combines a 2019 discussion paper and a draft guidance issued on September 15, 2023. It covers devices in six product codes, including intragastric implants, aspiration therapy devices, neuromodulators, oral removable retainers, ingested space-occupying devices and endoscopic suturing devices that alter gastric anatomy, RAPS reported.

Weight-loss thresholds by claim

The FDA recommends that pivotal studies include a pre-specified superiority margin for mean percent total body weight loss over a control group. For a "weight loss" indication, the guidance recommends a margin of at least 5%; for "limited weight loss," at least 2%. A margin below 2% may support a "weight management" indication if additional benefit is shown. Across all of these indications, the agency recommends that at least half of treated participants lose at least 5% of their total body weight.

A table in the guidance sorts weight-loss claims into four categories by the amount of weight lost and how long the device is used: short-term limited weight loss, limited weight loss, short-term weight loss and weight loss. The short-term categories cover six to under 12 months of use; the others cover 12 months or more. An "obesity treatment" indication should be supported by clinical benefits beyond weight loss alone, the guidance says.

Study design and benefit-risk

RAPS reported that the FDA recommends double-blind randomized controlled trials for pivotal studies supporting a weight-loss indication, with a sham control where scientifically feasible. For sham designs, the agency wrote: "We recommend the sham device and/or sham procedure be designed in a way to minimize the study participant's ability to determine whether they have the study device or the sham device."

Compared with the earlier documents, the final version adds clarifications on sham controls, discussion of statistical analysis using modified intent-to-treat populations, and patient-reported outcomes as a factor in benefit-risk evaluation, according to RAPS. It also points sponsors to the FDA's Q-Submission Program for feedback on planned studies.

In weighing benefits, the FDA said it will consider the amount of weight loss, improvements in cardiometabolic risk factors, reductions in obesity-related comorbidities and quality of life, RAPS reported. The agency says its recommendations "reflect current review practices of premarket submissions for these devices and are intended to promote consistency and facilitate efficient review of these submissions."

The guidance is filed under docket FDA-2019-N-4060. As with other FDA guidance, it contains nonbinding recommendations.