Phase 3 evaluation of HP802‐247 in the treatment of chronic venous leg ulcers

In 2012 we reported promising results from a phase 2 clinical trial of HP802‐247, a novel spray‐applied investigational treatment for chronic venous leg ulcers consisting of human, allogeneic fibroblasts and keratinocytes. We now describe phase 3 clinical testing of HP802‐247, its failure to detect efficacy, and subsequent investigation into the root causes of the failure. Two randomized, controlled trials enrolled a total of 673 adult outpatients at 96 centers in North America and Europe. The primary endpoint was the proportion of ulcers with confirmed closure at the end of 12 weeks of treatment. An investigation into the root cause for the failure of HP802‐247 to show efficacy in these two phase 3 trials was initiated immediately following the initial review of the North American trial results. Four hundred twenty‐one patients were enrolled in the North American (HP802‐247, 211; Vehicle 210) and 252 in the European (HP802‐247, 131; Vehicle 121) trials. No difference in proportion of closed ulcers at week 12 was observed between treatment groups for either the North American (HP802‐247, 61.1%; Vehicle 60.0%; p = 0.5896) or the European (HP802‐247, 47.0%; Vehicle 50.0%; p = 0.5348) trials. Thorough investigation found no likelihood that design or execution of the trials contributed to the failure. Variability over time during the trials in the clinical response implicated the quality of the cells comprising HP802‐247. Concordance between the two separate, randomized, controlled trials with distinct, nonoverlapping investigative sites and independent monitoring teams renders the possibility of a Type II error vanishingly small and provides strong credibility for the unexpected lack of efficacy observed. The most likely causative factors for the efficacy failure in phase 3 was phenotypic change in the cells (primarily keratinocytes) leading to batch to batch variability due to the age of the cell banks.     

Recommendations to Improve Payment Policies for Comprehensive Dementia Care

Access to comprehensive dementia care is limited. Recent changes in billing for professional services, including new physician fee schedule codes, encourage clinicians to provide new services; however, current reimbursement does not cover costs for all needed elements of dementia care. The Payment Model for Comprehensive Dementia Care Conference convened more than 50 national experts from diverse perspectives to review promising strategies for payment reform including ways to accelerate their adoption. Recommendations for reform included payments for services to family caregivers; new research to determine success metrics; education for consumers, providers, and policymakers; and advancing a population health model approach to tier coverage based on risk and need within a health system.     

Quality Measures for Supportive Cancer Care: The Cancer Quality-ASSIST Project

Patients and physicians often cite symptom control as one of their most important goals in cancer care. Despite this, a previous systematic review found few tools for evaluating the quality of supportive cancer management. We developed a comprehensive set of quality indicators for evaluating pain and nonpain symptom management as well as care planning needs in cancer patients. Based on the prevalence and quality-of-life data, clinician-researchers prioritized pain, psychosocial distress, dyspnea, nausea and vomiting, fatigue and anorexia, treatment-associated toxicities, and information and care planning for quality-indicator development. Using search terms and selection criteria, we identified English-language documents from Medline (1997–2007) and Internet-based searches. Based on this evidence, clinician-reviewers proposed process quality indicators. We then used the VA Health Services Research and Development (VA HSR & D) appropriateness methods to compile the ratings of a multidisciplinary, international expert panel of the validity and feasibility of each indicator. The panel judged 92 out of 133 (69%) proposed quality indicators valid and feasible (15 out of 23 pain, 5 out of 6 depression, 8 out of 11 dyspnea, 15 out of 19 nausea and vomiting, 13 out of 26 fatigue and anorexia, 23 out of 32 other treatment-associated toxicities, and 13 out of 16 information and care planning). Of the final indicators, 67 are potentially useful for inpatient and 81 for outpatient evaluation, and 26 address screening, 12 diagnostic evaluation, 20 management, and 21 follow-up. These quality indicators provide evidence-explicit tools for measuring processes critical to ensuring high-quality supportive cancer care. Research is needed to characterize adherence to recommended practices and to evaluate the use of these measures in quality improvement efforts.     

Availability of Gynecologic Services in the Department of Veterans Affairs

PURPOSE: The optimum approach to providing the Congressionally mandated gender-specific services for which women veterans are eligible is unknown. We evaluated onsite availability of gynecologic services, clinic type and staffing arrangements, and the impact of having a gynecology clinic (GYN) and/or an obstetrician gynecologist (OBGYN) routinely available. METHODS: We analyzed data from the 2001 national VHA Survey of Women Veterans Health Programs and Practices (n = 136 sites; response rate, 83%). We assessed availability of gynecologic services, and evaluated differences in availability by clinic type (designated women's health provider in primary care [PC], separate women's health clinic for primary care [WHC], and/or separate GYN) and staffing arrangements (OBGYN routinely involved versus not). MAIN FINDINGS: Out of 133 sites, 77 sites (58%) offered services through a GYN and 56 sites (42%) did not have GYN. Seventy-two (54%) sites had a WHC. More sites with an OBGYN provided endometrial biopsies (91% vs. 20%), IUD insertion (85% vs. 14%), infertility evaluation (56% vs. 23%), infertility treatment (25% vs. none), gynecologic surgery (65 vs. 28%), p < .01. In comparison to sites without WHC, those with WHC were more likely to offer services onsite: endometrial biopsy odds ratio (OR) 6.0 (95% confidence interval [CI], 2.0-18.1); IUD insertion 4.4 (1.6-12.2); infertility evaluation 2.8 (1.2-6.3); and gynecologic surgery 2.3 (1.0-5.4). CONCLUSION: As the VA develops strategic plans for accommodating the growing number of women veterans, leaders should consider focusing on establishing WHC for primary care and routine availability of OBGYN or other qualified clinicians, rather than establishing separate GYN.