FDA finalizes guidance on weight-loss devices
The US Food and Drug Administration (FDA) on Thursday finalized guidance to assist sponsors developing medical devices intended for weight loss at the premarket stage. This guidance provides information on non-clinical testing, clinical study design for these submissions, and outlines how the agency evaluates the benefit-risk analysis needed to support weight loss claims.The guidance combines a discussion paper released in 2019 and a draft guidance issued on 15 September 2023 concerning weight loss devices. FDA announced that the consolidation is intended to simplify usability, as both documents address the same type of products. (RELATED: Weight-Loss Devices: FDA Seeks Feedback on Benefit-Risk Considerations, Regulatory Focus 5 September 2019; FDA weight-loss device guidances address clinical and non-clinical studies, Regulatory Focus 18 September 2023)
The guidance pertains to devices categorized under six product codes, which include intragastric implants, aspiration therapy devices, neuromodulators, oral removable retainers, ingested space-occupying devices, and endoscopic suturing devices designed to alter gastric anatomy. FDA also indicated that new product codes or classification regulations may be established in the future.
FDA said that its guidance 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The agency considered the comments it received on the discussion paper and draft guidance. The final guidance now includes clarifications regarding the use of sham controls, discussions on statistical analysis using modified intent-to-treat populations, and the incorporation of patient-reported outcomes (PROs) as a factor in the benefit-risk evaluation. Additionally, more reference citations have been added, as well as references to FDA’s Q-Submission Program, which can be used to request feedback on the proposed clinical study design.
The guidance said that companies should submit their product code and the following information to FDA: a complete description of the device, which may be accompanied by engineering drawings. Sponsors should also include a description addressing how the device functions.
For devices containing nitinol, companies should consult FDA’s 2021 guidance Technical Considerations for Non-Clinical Assessment of Medical Devices Containing Nitinol.
Submitters should provide a description of the clinical study related to their device. This description should include details about the study design, such as whether randomization or blinding was used and what control groups were employed. Additionally, it should specify the number of participants enrolled in the study and how many investigational sites were involved, both in the US and internationally. Furthermore, the description should outline the primary study endpoints, present the results of the study, and indicate whether any adverse events were reported in connection with the use of the device.
FDA recommends that sponsors assess whether animal studies are necessary for non-clinical testing. These studies should focus on aspects that cannot be adequately evaluated through bench tests alone. Additionally, the design of these studies and their endpoints should be determined based on the intended use of the device and a clinical risk assessment.
The agency also recommends that sponsors actively engage in the Q-Submission Program to ensure that animal studies effectively address safety concerns.
FDA adds that pivotal studies supporting a weight loss indication should be conducted as double-blind, randomized controlled trials (RCTs). Additionally, the agency suggests including a sham-controlled study where scientifically feasible to minimize any potential placebo effect.
The guidance indicates that for first-in-kind devices, using a sham control in a clinical study can serve as an important comparator to assess the effectiveness of device against a placebo. “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,” FDA wrote.
To validate the device's effectiveness for weight loss, both the duration of use and the primary endpoint should indicate weight loss after at least 12 months. If the intended purpose is for short-term weight loss, the duration of use and the primary endpoint should show weight loss within six months.
FDA advises against using participants in studies who are unable or unwilling to follow the dietary restrictions specified in the clinical protocol. Additionally, these devices are not recommended for individuals with altered anatomy, such as those who have undergone sleeve gastrectomy. They are also not suitable for individuals with a history of dysmotility, delayed gastric emptying, or syndromes that are associated with recurrent vomiting.
The agency said it will weigh the benefits of a weight-loss device by considering several factors. These include the amount of weight loss associated with the device, improvements in cardiometabolic risk factors, and reductions in obesity-related comorbidities, such as significant decreases in HbA1c levels, hypertension, and dyslipidemia. Additionally, FDA said it will assess improvements in the quality of life.
Final guidance; Federal Register notice
