Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S.

End points in dermatologic clinical trials: A review for clinicians.

Clinical trials are critical for the development of new therapies in dermatology, and their results help determine US Food and Drug Administration (FDA) approval and guide care. Of special relevance is the clinical trial efficacy end point, the metric from which statistically significant outcome is derived. Clinicians' understanding of a clinical trial's end point is necessary for critical analysis of the trial results and for applying those results to daily practice.

Food and Drug Administration (FDA) drug approval end points for chronic cutaneous ulcer studies.

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.

The FDA and designing clinical trials for chronic cutaneous ulcers.

Treatment of chronic wounds can present a challenge, with many patients remaining refractory to available advanced therapies. As such, there is a strong need for the development of new products. Unfortunately, despite this demand, few new wound-related drugs have been approved over the past decade.

New drugs and new molecular entities in dermatology.

Objective: To identify and analyze the possible reasons that so few drugs with new molecular entities (NMEs) are first developed for "dermatologic diseases," especially diseases treated primarily by dermatologists.

Design: Systematic review and analysis. IMS Health (the pharmaceutical industry worldwide product database) was searched using the terms first launch, topical, and skin/dermatological for the preceding decade.

Evidence-based medicine, the research-practice gap, and biases in medical and surgical decision making in dermatology.

The objectives of this article are to promote a better understanding of a group of biases that influence therapeutic decision making by physicians/dermatologists and to raise the awareness that these biases contribute to a research-practice gap that has an impact on physicians and treatment solutions. The literature included a wide range of peer-reviewed articles dealing with biases in decision making, evidence-based medicine, randomized controlled clinical trials, and the research-practice gap. Bias against new therapies, bias in favor of indirect harm or omission, and bias against change when multiple new choices are offered may unconsciously affect therapeutic decision making.

Challenges encountered in dermatologic drug development.

Few truly new drugs are developed primarily for the treatment of dermatologic diseases. We discuss challenges and special considerations of dermatology drug development which contribute to this relative absence of novel drugs in dermatology. The issues considered are: a) the economic potential of dermatologic drugs including the potential return on investment (ROI); b) the benefit-to-risk ratio for treatments of skin disease; c) the relative absence of surrogate end points for topically applied drugs; d) drug penetration and vehicles; e) shelf life, stability, emulsifiers, preservatives; f ) contact irritancy, contact allergy, contact photoallergy and photocarcinogenicity; g) drugs with more than one active; h) semi-quantitative or soft primary end points; i) inadequate basic knowledge of pathophysiology of skin diseases.

A gene signature of nonhealing venous ulcers: potential diagnostic markers.

Background: Venous leg ulcers are responsible for more than half of all lower extremity ulcerations. Significant interest has been focused on understanding the physiologic basis on which patients fail to heal with standard therapy.

Objective: This study uses complementary DNA microarray analysis of tissue samples from healing and nonhealing venous leg ulcers to identify the genetic expression profiles from these dichotomous populations.

Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo.

A biofilm is a collection of microbial cells that are attached to a surface and embedded in a self-produced extrapolymeric substance. The understanding of the biofilm phenotype is important in the understanding of bacteria in vitro but it has been difficult to translate biofilm science to the clinical setting. More recently, preliminary criteria for defining biofilm associated diseases have been proposed and the purpose of this study was to create a biofilm-associated wound model based on these criteria.

Topical oxygen emulsion: a novel wound therapy.

Objective: To investigate the use of a topical oxygen emulsion (TOE), consisting of a supersaturated oxygen suspension using perfluorocarbon components, on second-degree burns and partial-thickness wounds.

Design: Oxygen is a required substance for various aspects of wound repair, and increased oxygen tension in a wound has been shown to stimulate phagocytosis and to reduce the incidence of wound infection. Second-degree burns and partial-thickness wounds were created on the backs of specific pathogen-free pigs.

Evaluation of Apligraf persistence and basement membrane restoration in donor site wounds: a pilot study.

Apligraf is a bilayered tissue-engineered product consisting of a bovine collagen matrix with neonatal fibroblasts, overlaid by a stratified epithelium containing living keratinocytes. The United States Food and Drug Administration has approved its use for venous leg ulcers and neuropathic diabetic foot ulcers. Apligraf provides a dermal matrix and produces cytokines similar to the human skin.

Over-the-counter topical antimicrobials: effective treatments?

There are many over-the-counter (OTC) bandage products available. In addition to their direct purchase by the public, many physicians provide OTC bandages to their patents after minor surgeries. The aim of this study was to evaluate in a well established porcine model the efficacy against Staphylococcus aureus of four OTC antimicrobial containing bandages as compared to two OTC ointments.

Venous ulcers: pathophysiology and treatment options.

Venous ulcers affect approximately 1% of the world's population, increasing healthcare expenditures and decreasing quality of life. Several hypotheses may help explain their origin. Incompetent veins or valves or impaired muscle function may lead to abnormal calf muscle pump function that can elevate ambulatory venous pressure (venous hypertension).

Cyanoacrylates for skin closure.

Cyanoacrylates (CAs) were not widely adopted for medical use until recently because of lingering concerns regarding the initial tissue toxicities of the short-chain CAs. The medium-chain CAs, primarily butyl-cyanoacrylate, have been widely used in Europe and Canada for several decades and have gone a long way in dispelling any lingering concerns about tissue toxicity. The newer, longer chain CA, octyl-2-cyanoacrylate (2-OCA), now has been approved for multiple uses in the United States and has achieved widespread acceptance by the medical and lay communities.