Empirical Investigation of Ethical Challenges Related to the Use of Biological Therapies.

The aim of this study was to investigate the ethical dilemma of prioritising financial resources to expensive biological therapies. For this purpose, the four principles of biomedical ethics formulated by ethicists Tom Beauchamp and James Childress were used as a theoretical framework. Based on arguments of justice, Beauchamp and Childress advocate for a health care system organised in line with the Danish system. Notably, our study was carried out in a Danish setting.

Advanced therapy medicinal products: value judgement and ethical evaluation in health technology assessment.

Advanced therapy medicinal products (ATMPs) are a heterogeneous class of medicinal products that by offering the potential of cure represent a paradigm shift in the approach of many life-threatening diseases. Although a common regulatory framework for ATMPs has been established in the EU, the health technology assessment (HTA) and financing decisions remain local. The aim of this article is to present an integrated analysis of the current status of the value judgment of ATMPs and the integration of ethical evaluation in the HTA process. It has been identified that approaching the specificities of ATMPs in terms of market access will require a broadening of the definition of value to be able to systematically capture elements of value not traditionally considered. Outcomes modelling will play an important role in the pricing and reimbursement of ATMPs, providing a way to bridge the gap caused by the absence of data from clinical studies or real-world data. Given the nature and disruptive consequences of ATMPs the assessment and adoption of these medicinal products raises important ethical questions, both at a policy and at society level that should be properly addressed. HTA can be made more transparent and reliable, and simultaneously promote robust and accountable decision making, by turning explicit the value judgments implicit in HTA. Ultimately, there should be no core conflict between ethical requirements and HTA in a scenario where the goal is to promote equity and access of patients to truly innovative therapies such as ATMPs, while assuring the sustainability of healthcare systems.

Vaginal Microbiota Transplantation: The Next Frontier.

The success of fecal microbiota transplantation (FMT) as a treatment for Clostrioides difficile infection (CDI) has stirred excitement about the potential for microbiota transplantation as a therapy for a wide range of diseases and conditions. In this article, we discuss vaginal microbiota transplantation (VMT) as "the next frontier" in microbiota transplantation and identify the medical, regulatory, and ethical challenges related to this nascent field. We further discuss what we anticipate will be the first context for testing VMT in clinical trials, prevention of the recurrence of a condition referred to as bacterial vaginosis (BV). We also compare clinical aspects of VMT with FMT and comment on how VMT may be similar to or different from FMT in ways that may affect research design and regulatory decisions.

Protective effects of amniotic fluid in the setting of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is the most common life threatening condition affecting preterm infants. NEC occurs in 1-5% of all neonatal intensive care admissions and 5-10% of very low birth weight infants. The protective role of human breast milk (BM) has been well established. It has also been shown that amniotic fluid (AF) and BM have many similarities in terms of presence of growth and other immune-modulatory factors. This finding led to the initial hypothesis that AF may exert similar protective effects against the development of NEC, as does BM. Multiple studies have elucidated the presence of growth factors in AF and the protective effect of AF against NEC. Studies have also described possible mechanisms how AF protects against NEC. At present, research in this particular area is extremely active and robust. This review summarizes the various studies looking at the protective effects of AF against the development of NEC. It also provides an insight into future directions, the vast potential of AF as a readily available biologic medium, and the ethical barriers that must be overcome before using AF.

Biological therapies for inherited diseases: social and bioethical considerations. Hemophilia as an example.

INTRODUCTION: In hemophilia, advanced therapies are warranted from a conceptual and methodological standpoint. Current advanced therapy strategies are centered on the use of adeno-associated viral vectors, although problems related to immunogenicity and hepatotoxicity still remain. AREAS COVERED: Future clinical trials will have to scrupulously observe international bioethical standards in terms of patient selection, particularly children. Patient recruitment rates are likely to remain low due to the stringent exclusion criteria usually imposed on the trial population regarding their hepatic and immunological markers and the presence of viral coinfection; and to the existence of an optimal palliative treatment. EXPERT OPINION: Accordingly, the results obtained are likely to be of low statistical significance, which could hinder their application to clinical practice. Another important issue is the degree to which society embraces these new emerging therapies. The unfamiliarity of society with these new methods, together with the many unresolved questions about them that remain, may threaten their acceptance not only by society at large but also by health-care professionals, which would limit their translational application to clinical practice.

Ethnic variations in the provision of biologic therapy for Crohn's disease: a Freedom of Information study.

In this study, we investigate whether the provision of biologic therapy for Crohn's disease is equitable across South Asian and English groups in NHS Trusts, which serve areas with significant ethnic variation. Data were requested from 10 NHS Trusts using a Freedom of Information (FOI) approach. Details of numbers of patients by ethnicity treated with infliximab or adalumimab for Crohn's disease between 2010 and 2012 were requested. Using population-based estimates of disease prevalence and Census data on population structure, observed and expected numbers who should have received treatment were calculated. In three Trusts, the number of South Asian patients who received such treatment was significantly less than British/White patients. These were: Pennine Acute Hospitals NHS Trust covering Oldham and North Manchester, Barking, Havering & Redbridge University Hospitals NHS Trust and University Hospitals of Leicester NHS Trust. The study is limited by several factors: 1. The only data available on prevalence in both English and South Asian communities comes from Leicester and was published in 1993. More recent data suggests that the prevalence of Crohn's disease now approaches 150/10(5) compared to the 76/10(5) for English patients which was recorded in Leicester. However, the two subsequent studies on prevalence which were published in 2000 from the North of England and 2010 from Scotland do not provide a breakdown by ethnicity. 2. The data were collected by administrative staff using a variety of approaches to their Trust's data bases and so the techniques used in each Trust are not comparable. In addition, studies from elsewhere suggest that the quality of FOI data is affected by the motivation of staff who collect the data. 3. With the exception of Leicester, there was no quality check on the accuracy of the data. In Leicester, 139 patients were on a register of biologic therapy and this compared with 343 patients reported by the FOI request. However, the proportions of patients by type of treatment and by ethnicity were comparable in the two data sets. This suggests that the data on ethnic differences reported by the FOI study reflects real differences. Clearly, there are South Asian communities where patients with Crohn's disease appear not to receive appropriate treatment in the form of biologics, and the reasons behind this need further consideration and investigation. We need to develop robust methods of monitoring the provision of biologic therapy across ethnic groups and communities. It is unacceptable for there to be a difference based on such grounds.

Cuestiones éticas y normativas de las investigaciones y terapias con células madre / Ethical and legal issues of stem cell research and therapy

Las investigaciones con células madre representan un desarrollo de vanguardia en la investigación biomédica que puede ofrecer un medio eficaz para tratar enfermedades que actualmente tienen pocas o ninguna opción de tratamiento. Estos avances han generado nuevas áreas para la investigación tanto a nivel académico como industrial y han planteado nuevos desafíos para la actual regulación de productuos terapéuticos. En el ámbio ético-jurídico, la investigación con células madre plantea dos grandes campos de problemas: los derivados de su obtención y los inherentes a su utilización. El marco normativo creado para regular una y otra problemática se ha efectuado por separado en la mayoría de las legislaciones nacionales, dado que comprometen decisiones normativas de diferente jerarquía. Identificaremos las principales cuestiones, tendencias y soluciones normativas que se plan teas a partir de estas nuevas tecnologías...

Role of biological therapy for inflammatory bowel disease in developing countries.

Inflammatory bowel disease (IBD) has become a global disease. Its incidence in developing countries is rising. In Asia, this has been attributed to the rapid modernisation and westernisation of the population. As IBD emerges in developing nations, there is a need to reconcile the most appropriate treatment for these patient populations from the perspectives of both disease presentation and cost. In the West, biological agents are the fastest-growing segment of the prescription drug market. They typically cost several thousand to several tens of thousands of dollars per patient per year. The healthcare systems in developing countries will struggle to afford such expensive treatments. Developing countries cover two-thirds of the earth's surface and are home to 3-5 billion inhabitants, constituting three-quarters of all humanity. If IBD emerges to the same extent in those countries as it has in the West, the need for biological therapy will increase dramatically, and the pharmaceutical industry, healthcare providers, patient advocate groups, governments and non-governmental organisations will have to discuss how to handle this. The authors propose that this dialogue should begin now with regard to (1) the major needs of patients with complicated IBD in developing countries, (2) the potential need for biological therapy in developing countries to treat IBD, (3) the necessary infrastructure for selecting patients with IBD who need biological therapy, and (4) medical/ethical issues limiting the use of biological therapy.

[Ethical aspects of human embryonic stem cell use and commercial umbilical cord blood stem cell banking. Ethical reflections on the occasion of the regulation of the European Council and Parliament on advanced therapy medicinal products]. / Bioethische und sozialethische Probleme bei der Verwendung von Geweben aus humanen embryonalen Stammzellen sowie der Aufbewahrung von Stammzellen aus dem Nabelschnurblut durch private Firmen zum autologen Gebrauch. Ethische Uberlegungen anlässlich der Verordnung (EG) Nr. 1394/2007 des europäischen Parlaments und des Rates über Arzneimittel für Neuartige Therapien.

The regulation of the European Council and Parliament on advanced therapy medicinal products also includes therapies with human embryonic stem cells. The use of these stem cells is controversially and heavily discussed. Contrary to the use of adult stem cells, medical and ethical problems concerning the use of human embryonic stem cells persists, because this use is based on the destruction of human life at the very beginning. The regulation foresees, therefore, subsidiarity within the European Member States. Although there are no ethical problems in principle with the use of stem cells from the umbilical cord blood, there are social ethical doubts with the banking of these stem cells for autologous use without any currently foreseeable medical advantage by commercial blood banks. Also in this case subsidiarity is valid.

The remains of the body: human tissue, competence and consent in an age of profit.

Over the past few decades human tissues and fluids have increasingly become of interest to health-oriented research due to their potential use in the development of new diagnostic tools, drugs and treatment modalities. They have also become valuable commodities that figure prominently in the recovery of hormones for cosmetic purposes, the production of proteins and in a whole range of uses in the biopharmacological industry. Unfortunately, current understanding of the ethical and legal status of human tissue and fluids, and of the conditions under which they may be recovered and used, is somewhat uneven. The aim of this presentation is to outline the ethical and legal considerations that must be met if a recovery and use protocol is to meet appropriate standards.