December 18, 2023
We appreciate the opportunity to comment on the FDA’s proposed guidance: “Diabetic Foot Infections: Developing Drugs for Treatment; Guidance for Industry.”
The National Center for Health Research (NCHR) is a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.
Diabetic foot infections are a serious public health issue that affects up to one third of diabetic patients and can lead to significant complications that drastically decrease the well-being and quality of life of these patients. However, the FDA’s draft proposal should acknowledge the growing body of evidence to suggest that not all diabetic foot infections require systemic antibiotic medications and that topical antibiotic solutions may be appropriate in some cases. NCHR strongly recommends that the FDA include information regarding topical treatments for diabetic foot infections and be more cautious about recommending any novel antibiotics being prescribed that have not been proven to be effective specifically for diabetic foot infections. In cases when they are prescribed, it should be part of a multidisciplinary medical decision.
Recent evidence has shown that Hispanic Americans and Indigenous populations are more likely to experience wound ulceration compared to non-Hispanic white Americans. Evidence has also demonstrated that African American patients are more likely to undergo an amputation for a diabetic foot infection when compared to non-Hispanic white Americans. Together, these data reflect discrepancies in treatment response, prognosis, and definitive management among diabetic patients with foot infections. Thus, NCHR strongly recommends that the FDA include racial and ethnic diversity as part of its Drug Development Population criteria. It is imperative that novel antibiotic medications are tested across a heterogeneous diabetic patient population with sufficient numbers of patients in various demographic groups to fully understand the safety, efficacy, and limitations of their use across the entire diabetic population.
Most important, given the severe implications that antimicrobial resistance has on public health, we disagree that non-inferiority trials should be accepted as evidence; instead, superiority trials should be required for the treatment of diabetic foot infections. We also recommend that superiority trials use direct patient reported outcomes of symptoms and function as an endpoint over the use of clinician reported outcomes. Novel antibiotics should be required to demonstrate superiority to standard antibiotic treatment. There would be no clinical benefit of using a novel antibiotic that has the same efficacy as the standard of care and it would harm public health, as it would further potentiate antimicrobial resistance.
It is important that the FDA focus on the clinical context of diabetic foot infections within the greater framework of public health, which this guideline fails to do. We urge that the FDA involve a wide breadth of stakeholders and experts in diabetic care, infectious disease, and public health in order to develop a more meaningful draft guidance that addresses both the need for novel antibiotic treatments for diabetic foot infections as well as the need to prevent further antibiotic resistance.