title: Food and Drug Administration (FDA) drug approval end points for chronic cutaneous ulcer studies.
abstract: The rising costs of caring for chronic cutaneous ulcers (CCUs) and recent appreciation of the mortality of CCUs have led to consideration of the reasons for the failure to have new drug therapies. No new chemical entities to heal CCUs have been approved by the Food and Drug Administration (FDA) in over a decade, in part due to an inability to reach the FDA accepted end point of "complete wound closure." The frequent failure to reach the complete closure end point brings forward the question of the relevance of other healing end points such as improved quality of life, or partial healing. Because CCUs carry a prognosis and mortality rate worse than many cancers, it is reasonable to compare the FDA trial end points for cancer drug approval with those for CCUs. And the difference is quite striking. While there is only one end point for CCUs, there are five surrogate and three direct end points for cancers. In contrast to cancer, surrogate end points and partial healing are not acceptable for therapies aimed at CCUs. For example, making tumors smaller is an acceptable end point, but making CCUs smaller is not and improvement in the signs and symptoms of cancer is an acceptable end point for cancers but not CCUs. As CCUs carry a prognosis and mortality rate worse than many cancers, we believe a reconsideration of end points for CCUs is highly warranted.
authors.affiliation: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA. weaglstein@gmail.com
authors.forename: William H
authors.initials: WH
authors.lastname: Eaglstein
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kirsner
authors.forename: Martin C
authors.initials: MC
authors.lastname: Robson
mesh_terms: D000671:Amputation, Surgical; D002908:Chronic Disease; D015897:Comorbidity; D003863:Depression / Q000209:etiology; D017277:Drug Approval; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008297:Male; D011183:Postoperative Complications / Q000188:drug therapy / Q000401:mortality*; D011379:Prognosis; D011788:Quality of Life; D018805:Sepsis / Q000209:etiology / Q000401:mortality; D012883:Skin Ulcer / Q000188:drug therapy / Q000401:mortality*; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration; D014945:Wound Healing; D014946:Wound Infection / Q000188:drug therapy / Q000401:mortality*