High-risk medical devices intended to help obese patients lose weight should result in more weight loss than lower-risk methods, an FDA advisory panel said last week
"For a 1-and-done [a permanently implanted device], or a device equivalent to a gastric bypass, you should have higher expectations of the weight loss," said panelist Dr. Steven Schwaitzburg, of Harvard Medical School. "Whereas, if we have lower-risk devices and are able to establish other types of endpoints like bridge [to surgery], exercise, etc., then [a lower bar for excess weight loss would be acceptable]."
Treating obese patients has a high public health impact, but obesity treatments present difficult trade-offs, the FDA’s gastroenterology and urology devices advisory panel underscored during the meeting May 10-11 in Gaithersburg, Md.
Obesity has reached epidemic proportions in the U.S., more than doubling since 1960. Some 36% of adults are categorized as obese, as are 18.1% of adolescents and 19.6% of children 6-11, according to the National Institutes of Health and the Journal of the American Medical Assn.
The federal watchdog agency panel noted that obesity is associated with more than 70 co-morbidities, including Type II diabetes, hypertension, dyslipidemia, coronary heart disease, cancers (endometrial, breast and colon), stroke, liver and gall bladder disease, sleep apnea and respiratory problems, osteoarthritis, and gynecological problems such as abnormal menses and infertility.
A broad array of potential devices with diverse benefit-risk profiles are available, according to the panel. For example, a study released at the annual meeting of the American College of Cardiology in Chicago in March found that gastric bypass and sleeve gastrectomy devices may be more effective in treating Type II diabetes than medication, a potential boon for device makers Allergan (NYSE:AGN), Johnson & Johnson (NYSE:JNJ) subsidiary Ethicon-EndoSurgery and GI Dynamics (ASX:GID).
Panelists overall recognized that patients struggling with obesity need more options. Since 1985, FDA has only approved 3 medical devices for the treatment of obesity, although device innovation has continued in this area, according to the agency. Only 2 of these devices remain on the market – Allergan’s Lap Band and Ethicon EndoSurgery’s Realize adjustable gastric band, both Class III devices.
The 3rd device, the Garren-Edwards gastric bubble, was pulled in 1992 by American Edwards Laboratories (now Edwards Lifesciences (NYSE:EW)) after 7 years on the U.S. market. Significant problems with spontaneous deflation of the bubble requiring surgical explant were reported during its 1st year on the market. The FDA says it worked to resolve the problems by proposing device and labeling changes, as well as enhanced physician training, and chose to restrict implantation to 3 months (down from 4) and limit its use to morbidly obese patients.
Post-market safety and effectiveness studies showed that the Garren-Edwards bubble was of no added benefit compared to sham insertion when combined with standard weight loss programs. Sales of the device began to taper and by 1988 effectively off the market.
Panelist Recommendations, Acceptable Risk
Panelists at last week’s hearing agreed that% excess weight loss, measured using body mass index of 18.5-25 kg/m2 as normal weight, is the best way to track weight loss from obesity devices, rather than another measure, like total body weight loss. Patients from 25-29.9 kg/m2 are considered overweight; a patient with a BMI of 30 kg/m2 or higher is labeled obese. Obese patients are further divided into 3 classes: Mild (BMI of 30.0-34.9 30 kg/m2), moderate ( BMI of 35.0-39.9 kg/m2) and severe (BMI of 40 kg/m2 or more).
"Almost any weight loss creates some good, in terms of co-morbidities," noted panel chairman Dr. Mark Talamini, chairman of the surgery department at the University of California, San Diego.
Although the FDA has focused on clinical trials for patients with BMIs of 40 kg/m2 or higher with no co-morbidities and BMIs of 35-40 kg/m2 with co-morbidities, because this group may have more to benefit from a weight-loss device, panelists agreed that it’s acceptable to test devices in patients with moderately increased BMI to prevent patients from becoming morbidly obese in the first place.
A majority of panelists did not believe that, in order to receive a medical device for weight loss, patients necessarily should have already failed diet and exercise. While panelists recognized that behavior modification does play a role, they noted that it "is not that effective over time." Additionally, the self-esteem boost from a temporary weight loss device may motivate them to keep the weight off in the future, panelists noted.
While randomized controlled study design has long been the gold standard in demonstrating effectiveness in medical intervention, implanting an ineffective sham device to meet these ends raises ethical concerns. Patients receiving sham implants could be harmed without any potential for medical benefit; panelists were roughly split on whether the agency should require shams to prove clinical effectiveness. But a majority agreed that shams are appropriate for first-in-kind devices.
To give companies developing weight loss devices a better idea of risk category, the FDA established a framework to assess risk based on rates of expected and unexpected events. The agency defined 11 event categories for each of 3 bariatric device classes.
For example, the FDA suggested that Level 2 devices may result in short/long term health consequences of malabsorption or development of an eating disorder, or tissue damage not requiring an operation (such as erosion, ulcer, GI or esophageal mucosal bleeding) in less than 20% of cases. Hospitalization without surgery is permissible less than 5% of the time for Level 2 devices, and less than 1% when surgery is required. Any devices with higher risk numbers than that rank as Level 3.
Panelists said they found the framework acceptable as a starting point, but suggested FDA make infection a separate category.
Determining what level of risk patients themselves are willing to undertake could help narrow the risk parameters, though panelists cautioned that surgeons ultimately have to be willing to accept risk when taking a patient’s life in their hands. The FDA said it put together a survey to assess patient risk tolerance it hopes to complete electronically, perhaps via social networking sites. Panelists said they were concerned about adjusting acceptable risk based on patients’ stated risk tolerance. The risk tolerance data could help adjust the benefits side in favor of device seeking agency approval, however, according to the panel.