Systematic review of economic evaluations of human cell-derived wound care products for the treatment of venous leg and diabetic foot ulcers

<p>Abstract</p> <p>Background</p> <p>Tissue engineering is an emerging field. Novel bioengineered skin substitutes and genetically derived growth factors offer innovative approaches to reduce the burden of diabetic foot and venous leg ulcers for both patients and health care systems. However, they frequently are very costly. Based on a systematic review of the literature, this study assesses the cost-effectiveness of these growth factors and tissue-engineered artificial skin for treating chronic wounds.</p> <p>Methods</p> <p>On the basis of an extensive explorative search, an appropriate algorithm for a systematic database search was developed. The following databases were searched: BIOSIS Previews, CRD databases, Cochrane Library, EconLit, Embase, Medline, and Web of Science. Only completed and published trial- or model-based studies which contained a full economic evaluation of growth factors and bioengineered skin substitutes for the treatment of chronic wounds were included. Two reviewers independently undertook the assessment of study quality. The relevant studies were assessed by a modified version of the Consensus on Health Economic Criteria (CHEC) list and a published checklist for evaluating model-based economic evaluations.</p> <p>Results</p> <p>Eleven health economic evaluations were included. Three biotechnology products were identified for which topical growth factors or bioengineered skin substitutes for the treatment of chronic leg ulceration were economically assessed: (1) Apligraf^®, a bilayered living human skin equivalent indicated for the treatment of diabetic foot and venous leg ulcers (five studies); (2) Dermagraft^®, a human fibroblast-derived dermal substitute, which is indicated only for use in the treatment of full-thickness diabetic foot ulcers (one study); (3) REGRANEX^®Gel, a human platelet-derived growth factor for the treatment of deep neuropathic diabetic foot ulcers (five studies). The studies considered in this review were of varying and partly low methodological quality. They calculated that due to shorter treatment periods, fewer complications and fewer inpatient episodes the initial cost of the novel biotechnology products may be offset, making the treatment cost-effective or even cost-saving. The results of most studies were sensitive to initial costs of the products and the evidence of effectiveness.</p> <p>Conclusion</p> <p>The study results suggest that some growth factors and tissue-engineered artificial skin products feature favourable cost-effectiveness ratios in selected patient groups with chronic wounds. Despite the limitations of the studies considered, it is evident that health care providers and coverage decision makers should take not only the high cost of the biotechnology product but the total cost of care into account when deciding about the appropriate allocation of their financial resources. However, not only the cost-effectiveness but first of all the effectiveness of these novel biotechnology products deserve further research.</p

Karl Homann aus Perspektive kohärentistischer Wirtschaftsethik

Abstract (German version follows): This paper develops a new proposal for a coherentist business ethic in which ethically justified and empirically supported proposed solutions to economic problems are developed through a coherentist process of adjustments between the three levels of (1) conception of problem and its solution, (2) positive economic theory, and (3) ethical theories. Using an example, it illustrates how in this framework, Homann's business ethics gains in validity and relevance but loses its claim to universality. // Diese Arbeit entwickelt eine kohärentistische Wirtschaftsethik, in der ethisch begründete und empirisch gestützte Lösungsvorschläge für ökonomische Probleme durch einen kohärentistischen Anpassungsprozess zwischen den drei Ebenen (1) Auffassung von Problem und Lösungsansatz, (2) positive ökonomische Theorie, sowie (3) ethischen Theorien erarbeitet werden. Anhand eines Beispiels wird illustriert, wie Homanns Wirtschaftsethik in diesem Rahmen an Validität und Relevanz gewinnt, jedoch ihren Universalitätsanspruch verliert

Clearing up the hazy road from bench to bedside: A framework for integrating the fourth hurdle into translational medicine

<p>Abstract</p> <p>Background</p> <p>New products evolving from research and development can only be translated to medical practice on a large scale if they are reimbursed by third-party payers. Yet the decision processes regarding reimbursement are highly complex and internationally heterogeneous. This study develops a process-oriented framework for monitoring these so-called fourth hurdle procedures in the context of product development from bench to bedside. The framework is suitable both for new drugs and other medical technologies.</p> <p>Methods</p> <p>The study is based on expert interviews and literature searches, as well as an analysis of 47 websites of coverage decision-makers in England, Germany and the USA.</p> <p>Results</p> <p>Eight key steps for monitoring fourth hurdle procedures from a company perspective were determined: entering the scope of a healthcare payer; trigger of decision process; assessment; appraisal; setting level of reimbursement; establishing rules for service provision; formal and informal participation; and publication of the decision and supplementary information. Details are given for the English National Institute for Health and Clinical Excellence, the German Federal Joint Committee, Medicare's National and Local Coverage Determinations, and for Blue Cross Blue Shield companies.</p> <p>Conclusion</p> <p>Coverage determination decisions for new procedures tend to be less formalized than for novel drugs. The analysis of coverage procedures and requirements shows that the proof of patient benefit is essential. Cost-effectiveness is likely to gain importance in future.</p

Points to consider for prioritizing clinical genetic testing services: a European consensus process oriented at accountability for reasonableness.

Given the cost constraints of the European health-care systems, criteria are needed to decide which genetic services to fund from the public budgets, if not all can be covered. To ensure that high-priority services are available equitably within and across the European countries, a shared set of prioritization criteria would be desirable. A decision process following the accountability for reasonableness framework was undertaken, including a multidisciplinary EuroGentest/PPPC-ESHG workshop to develop shared prioritization criteria. Resources are currently too limited to fund all the beneficial genetic testing services available in the next decade. Ethically and economically reflected prioritization criteria are needed. Prioritization should be based on considerations of medical benefit, health need and costs. Medical benefit includes evidence of benefit in terms of clinical benefit, benefit of information for important life decisions, benefit for other people apart from the person tested and the patient-specific likelihood of being affected by the condition tested for. It may be subject to a finite time window. Health need includes the severity of the condition tested for and its progression at the time of testing. Further discussion and better evidence is needed before clearly defined recommendations can be made or a prioritization algorithm proposed. To our knowledge, this is the first time a clinical society has initiated a decision process about health-care prioritization on a European level, following the principles of accountability for reasonableness. We provide points to consider to stimulate this debate across the EU and to serve as a reference for improving patient management

Was Germany ever united? Evidence from intra- and international trade 1885–1933

When did Germany become economically integrated? Within the framework of a gravity model, based on a new data set of about 40,000 observations on trade flows within and across the borders of Germany over the period 1885 – 1933, I explore the geography of trade costs across Central Europe. There are three key results. First, the German Empire before 1914 was a poorly integrated economy, both relative to integration across the borders of the German state and in absolute terms. Second, this internal fragmentation resulted from cultural heterogeneity, from administrative borders within Germany, and from geographical barriers that divided Germany along natural trade routes into eastern and western parts. Third, internal integration improved, while external integration worsened after World War I and again with the Great Depression, in part because of border changes along the lines of ethno-linguistic heterogeneity. By the end of the Weimar Republic in 1933, Germany was reasonably well integrated

European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death.

Sudden cardiac death (SCD) accounts for 10-20% of total mortality, i.e., one in five individuals will eventually die suddenly. Given the substantial genetic component of SCD in younger cases, postmortem genetic testing may be particularly useful in elucidating etiological factors in the cause of death in this subset. The identification of genes responsible for inherited cardiac diseases have led to the organization of cardiogenetic consultations in many countries worldwide. Expert recommendations are available, emphasizing the importance of genetic testing and appropriate information provision of affected individuals, as well as their relatives. However, the context of postmortem genetic testing raises some particular ethical, legal, and practical (including economic or financial) challenges. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with international experts, developed recommendations on management of SCD after a workshop sponsored by the Brocher Foundation and ESHG in November 2016. These recommendations have been endorsed by the ESHG Board, the European Council of Legal Medicine, the European Society of Cardiology working group on myocardial and pericardial diseases, the ERN GUARD-HEART, and the Association for European Cardiovascular Pathology. They emphasize the importance of increasing the proportion of both medical and medicolegal autopsies and educating the professionals. Multidisciplinary collaboration is of utmost importance. Public funding should be allocated to reach these goals and allow public health evaluation

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)