How To Measure Outcomes in Obesity TreatmentsFriday, August 24, 2012
Rather, the whole point of treating obesity is to improve health and well-being.
Thus, although excess weight is a risk factor and contributor to a wide range of health problems, not everyone who meets BMI criteria for obesity necessarily has (or will develop) these problems. Also, simply losing weight does not necessarily translate into better health.
These facts provide a particular challenge when it comes to assessing the benefits and risks of obesity treatments – a problem of considerable interest to regulators, who have to make decisions about whether or not new obesity treatments provide important health benefits or not.
In an effort to explore the pressing issues and challenges surrounding FDA approval and appropriate use of drugs to treat obesity, The George Washington University School of Public Health and Health Services Department of Health Policy convened the “Obesity Drugs Outcome Measures Dialogue Group,” a group of diverse stakeholders who met to identify the key issues surrounding the evaluation of pharmaceutical interventions for the treatment of obesity. Members of the group included clinicians specializing in adult and pediatric obesity; leaders from patient and consumer groups; public health organizations and industry representatives; and researchers from academia (see list on page two). Officials from the FDA, CDC, and NIH also observed and provided background information to the group to help inform the process (government officials were not asked to endorse or sign on to this final report).
The consensus report of this group has now been released and should be of interest to any one involved in the design and interpretation of obesity interventions.
The report is structured as a series of “Findings” and “Considerations” grouped into six general categories. The following summarises the ‘Considerations’ for each of these categories:
1. Understanding Obesity: Pharmacological interventions under investigation for the clinical treatment of obesity should be approached as obesity treatments rather than weight loss agents.
2. Characterizing the Population: More sophisticated criteria should be employed to characterize individuals at different levels of health, feeling, and functioning impairment, to determine appropriate patient-centered benefits and risks analysis.
3. The Need for Additional Treatments for Obesity: When the FDA determines that the benefits of taking a particular drug outweigh its risks in treating obesity, that drug should be available for clinical use in patients where such use is safe and medically appropriate. Although obesity drugs may not be safe or suitable options for all individuals wishing to use them, it is important that safe and effective drugs be made available as treatment options for individuals with obesity that require an alternative or additional weight loss intervention to diet, exercise, or surgery.
4. Limiting or Mitigating the Risk of Medically Inappropriate or Unsafe Use of Obesity Drugs: Given the concern over medically inappropriate or unsafe use of obesity drugs by those for whom the risks outweigh the benefits, the FDA could potentially employ a mechanism, such as Risk Evaluation and Mitigation Strategies (REMS) or an alternative, that will allow drug approval, distribution, and use solely for those for whom the drug is indicated.
5. Limitations in the Current FDA Approval Process, and Altering the Risk-Benefit Framework for Evaluation of Obesity Drugs: Individuals with obesity are not all alike; in evaluating the benefits and risks of obesity-related treatments, patients at different points on the obesity spectrum should be viewed separately. Higher risk of adverse effects of drugs may be acceptable for individuals with more severe obesity and comorbidities. The FDA could consider evaluating the risks and benefits of obesity drugs across several different patient profiles and could tailor approval decisions, combined with risk mitigation strategies described above, to allow access to the drug for those patients with obesity for whom the benefits of the drug outweigh its risks. To effectively address patient perspectives in making obesity drug approval decisions, tools to measure QoL or PROs that are acceptable to the FDA for regulatory measures need to be developed and utilized in the immediate future. 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. The FDA should update its Guidance to Industry to include improvements in feeling and functioning domains, for which validated means of measuring such improvements exist, as appropriate and optional secondary endpoints.
6. Special Considerations regarding Pediatric Patients with Obesity: Unique ethical and practical issues come into play when studying any drug in children. However, when these issues can be resolved appropriately, children and adolescents should be included in clinical trials for obesity drugs once safety concerns have been addressed. Pediatric patients with severe obesity could be considered candidates for drug therapy after the failure of more conservative therapies. The government and/or research community should prioritize development of a registry of children and adolescents who have been treated with obesity drugs for an extended period of time to assess long-term outcomes and side effects.
The document also lists measures to determine long-term, intermediate, and immediate outcomes of obesity treatment that should be considered in obesity treatment trials.
Not only, do I wholeheartedly agree with the overall recommendations of this document, but I was also delighted to see a direct mention and discussion of the Edmonton Obesity Staging System (EOSS) as a possible approach to better characterising obese individuals. In fact, the appendix of this document includes a copy of our EOSS staging tool.
While it is hard to determine the ultimate impact of these recommendations, it is indeed reassuring to see many of the issues raised in these postings reflected in this document.