FDA weight-loss device guidances address clinical and non-clinical studies

A decade in the making, the US Food and Drug Administration (FDA) has published two complementary draft guidances for sponsors developing weight-loss devices. The documents outline the agency’s thinking on the types of studies that are appropriate for premarket applications, trial endpoints, safety data, ethical considerations, and special considerations for pediatric populations.

FDA published the two draft guidances on 15 September, outlining its thinking on clinical and non-clinical studies that sponsors should conduct before submitting their premarket applications. More specifically, the agency offers recommendations on non-clinical testing, clinical study designs, and how it will evaluate risk-benefit depending on the treatment (RELATED: Weight-Loss Devices: FDA Seeks Feedback on Benefit-Risk Considerations, Regulatory Focus 5 September 2019)

For now, the guidances apply to six product codes, including intragastric implants, aspiration therapy systems, neuromodulators, and specific ingested space-occupying devices. New product codes and classification regulations may be added to the guidances in the future, FDA noted.

Clinical study guidance

In its guidance covering clinical study expectations, FDA noted that obesity and weight loss may be affected by demographics, culture, and public health policies, which means that studies for devices intended for US patients should focus on collecting domestic data.

“FDA has encountered challenges about the applicability of foreign effectiveness data to the U.S. population for devices with indications associated with weight loss,” FDA wrote in the guidance. “Therefore, we recommend that pivotal studies be conducted in the U.S.”

In cases where foreign data is collected, FDA recommended that no more than 50% of the pivotal study data come from outside the US and no more than 20% of the total enrollment population be from a single site.

Ideally, FDA wants sponsors to run double-blinded, randomized controlled trials (RCT) when conducting pivotal studies. Additionally, the agency recommends that staff who are not directly conducting the studies, such as dieticians and those collecting data, stay blinded throughout the study.

The agency recommended sham-controlled studies for these devices since a placebo effect is anticipated. However, FDA noted that a sham control may not be appropriate in all cases. “If a sham device or sham procedure is not appropriate for a clinical trial design, we recommend a concurrent control arm where the control and treatment groups follow the same lifestyle programs,” FDA wrote in the draft guidance.

Considering the increased risks associated with implanted or surgically-placed devices, FDA argued that trial participants should be eligible after they have failed more conservative treatments such as diet, exercise, and behavior modification.

In recent years, the FDA’s Center for Devices and Radiological Health (CDRH) has become more open to factoring in patient-reported outcomes (PRO) and patient-preference information (PPI) when deciding on whether to allow a product to enter the market. The agency has published a guidance on this topic and in the latest guidance noted that sponsors should consider including PRO and PPI in their product submissions (RELATED: Patient preference information: Researchers offer insights on medical device clinical trial design, Regulatory Focus 6 September 2022)

“The value patients associate with the treatment, their willingness to accept the risk of this treatment to achieve the benefit, the treatment’s ability to improve the patient’s overall quality of life, and the patient’s ability to understand the benefits and risks of the treatments are important factors in evaluating device benefit,” FDA wrote in the clinical study guidance.

The clinical study guidance also addresses considerations for pediatric trials, including determining suitability for participation. “The increased prevalence of children being overweight or having obesity, emphasizes an unmet need to provide therapy to children who have a disease that impacts their health, quality of life, and psychosocial factors,” the agency wrote. “FDA remains open to considering risk-based clinical study designs and intends to consider both the benefits and risks to adolescent study participants when determining the amount of benefit-risk evidence needed before initiation of an adolescent weight-loss device study.”

The clinical study guidance addresses additional factors such as justifying treatment parameters, developing safety and effectiveness endpoints, reporting adverse events, and benefit-risk considerations.

Non-clinical testing guidance

The non-clinical guidance addresses how weight-loss devices should be labeled, the level of sterilization they should conform to, understanding their pyrogenicity, and potential safety concerns about their electric and electromagnetic fields, among others.

In the guidance, FDA notes that due to limitations of bench models, there may be instances when animal studies may be needed to demonstrate the safety and efficacy of the device in the product application. These in vivo studies can help regulators better understand the product’s physiological, pathological, and toxicological effects.

“We recommend submitters assess whether an animal study(ies) is warranted in the non-clinical testing plan. Study in an animal model should address factors that cannot be evaluated through bench tests alone,” FDA wrote. “The study design and endpoints should be based upon the intended use of the device and clinical risk assessment.”

While there may not be any single animal study design that can be used as a template for these non-clinical studies, sponsors should use the agency’s 3Rs principle to “replace, reduce and/or refine animal use” in their research, according to FDA.

FDA also encouraged sponsors to use the Q-Submission process to engage early about their study plans and to consult with the agency to examine non-animal testing methods that may be able to arrive at the same data.

Stakeholders can comment on the guidances on regulations.gov under docket no. FDA-2019-N-4060 until 14 November.

Draft guidance for weight-loss devices - clinical studies
Draft guidance for weight-loss devices – non-clinical studies

FDA weight-loss device guidances address clinical and non-clinical studies

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