Measures that take into account the effects of weight loss on specific areas of "feeling and function" should be included in the evaluation of drugs being developed to treat obesity, according to a report on obesity drug outcome measures, released by the George Washington University School of Public Health and Health Services.
"The FDA should consider patient improvements in feeling and function associated with weight loss as part of the risk-benefit calculus in its evaluation of drugs for the treatment of obesity where data are provided demonstrating benefit in a drug-specific clinical trial," concludes the report, called "Obesity Drug Outcome Measures."
The specific areas that can be measured using validated tools include osteoarthritis, mobility, and urinary incontinence, and could be considered secondary end points for obesity drug trials, the report pointed out.
The report is a result of the discussions and recommendations made by stakeholders convened by GWU – which included clinicians who treat obesity, Food and Drug Administration officials who review these drugs, patient advocates, and pharmaceutical companies – to evaluate the issues and challenges related to FDA approval of drugs for obesity and the appropriate use of obesity drugs, including the need for more treatments to help fill the void between lifestyle interventions and bariatric surgery.
Copyright George Washington University
Dr. Donna Ryan
The risks associated with a drug treatment may be more acceptable to an obese patient with "feeling and function abnormalities," Dr. Donna Ryan said during a webinar to discuss the report. Dr. Ryan, who is involved in clinical trials and research of obesity at the Pennington Biomedical Research Center, Baton Rouge, La., noted that one of the main focuses of the panel was on the various conditions that can be improved with modest weight loss, and cited a study that found a modest amount of weight loss at 1 year was associated with improvements in urinary incontinence. The effect of weight loss on improvements in sleep apnea was also mentioned during the webinar.
Among the other recommendations in the report were considering the drugs for chronic weight management as obesity treatments, not weight loss drugs, and limiting the availability of these drugs to people "for whom they are medically appropriate," and studying obesity drugs in pediatric patients.
Currently, the FDA’s draft guidance for industry for developing products for weight management are based on changes in body weight, as a primary end point, and changes in cardiometabolic parameters, as a secondary end point. The guidance, used since 2007, states that a drug can be considered effective if after 1 year of treatment, the difference in mean weight loss between patients treated with the product and those treated with placebo is at least 5% and the difference is statistically significant; or the proportion of subjects who lose at least 5% of their baseline body weight on the active product is at least 35%, is about double the proportion in the placebo-treated group – and the difference between the groups is statistically significant.
The FDA does not accept any quality of life or patient-reported outcome measurements when considering obesity drugs for approval, because the tools that measure these outcomes do not meet the agency’s standards.
The research project was supported by unrestricted gifts from Eisai Co.; Novo Nordisk Worldwide; Obesity Action Coalition; Orexigen Therapeutics; Takeda Pharmaceuticals, USA; and Vivus.