Post-COVID-19 Lung Transplantation Italian Pivotal Protocol: Some Ethical Considerations.

SARS­CoV­2 mostly affects the respiratory system with clinical patterns ranging from the common cold to fatal pneumonia. During the first wave of the COVID-19 pandemic, owing to the high number of patients who were infected with SARS­CoV­2 and subsequently recovered, it has been shown that some patients with post-COVID-19 terminal respiratory failure need lung transplantation for survival. There is increasing evidence coming from worldwide observations that this procedure can be performed successfully in post-COVID-19 patients. However, owing to the scarcity of organs, there is a need to define the safety and efficacy of lung transplant for post-COVID-19 patients as compared to patients waiting for a lung transplant for other pre-existing conditions, in order to ensure that sound ethical criteria are applied in organ allocation. The Milan's Policlinic Lung Transplant Surgery Unit, with the revision of the National Second Opinion for Infectious Diseases and the contribution of the Italian Lung Transplant Centres and the Italian National Transplant Centre, set up a pivotal observational protocol for the lung transplant of patients infected and successively turned negative for SARS­CoV­2, albeit with lung consequences such as acute respiratory distress syndrome or some chronic interstitial lung disease. The protocol was revised and approved by the Italian National Institute of Health Ethics Committee. Description of the protocol and some ethical considerations are reported in this article.

From Experimental Technique to Clinical Practice: Which Pathway in Transplant Surgery?

The question of whether a medical procedure is to be considered experimental or routine practice has enormous practical implications. In transplant surgery, as compared with pharmacologic clinical trials, the transition from experimental procedure to normal care is far from clear cut. Clinical trials comprise 4 well-established phases of evaluation going from phase I, aimed at assessing safety and identifying side effects in a few healthy volunteers, to phase IV, which involves entire populations and is aimed at long-term postmarketing surveillance. In transplant surgery, technical progress and experimentation follow more atypical and individual routes. As compared with pharmacologic research, the decision about "routine practice readiness" of a surgical procedure does not rely on a standardized formal act but rather on experts' capacity to find a consensus based on best practices and on ad-hoc criteria as well. Independent assessment by a panel of experts and oversight by an institutional review board are key to facilitating meaningful protection of transplant recipients and allowing the research to go forward. The framework of the human subjects protection regulations should also consider the transplant of organs that have previously been part of a research project.

Ethical Issues in Uterine Transplantation: Psychological Implications and Informed Consent.

Since 2000, 13 uterine transplantations (UTxs) have been performed in women with absolute uterine infertility factor (AUIF), from both living and deceased donors, in different transplantation centers worldwide. At present the birth of 4 children following UTx is documented by the literature, and a woman was having a second pregnancy in October 2015. Following these successes it is likely that the procedure will become part of normal healthcare practice, even though at the moment it is still experimental and, as such, requires careful attention. Because the emotional aspects that are tied to UTx may foster the "therapeutic misconception" of participants, which consists in an overestimation of the benefits and an underestimation of the risks, careful attention should be paid also to informed consent (IC), which must include the following: describing techniques, pointing out risks and possibility of failure, and informing about the treatments required after the intervention. Because the final aim of UTx is the birth of a healthy child, the IC document must include details not only of the transplantation itself, but also of the very particular pregnancy deriving from it, and the need to remove the uterus following delivery(ies) to avoid these risks. Here we suggest that the IC process includes counselling techniques, possibly involving the psychologist that is part of the transplantation team, to target the information and decision-making process to the specific situation of each couple.

The current situation and needs of rare disease registries in Europe.

BACKGROUND: Registries are considered key instruments for developing rare disease (RD) clinical research, enhancing patient care and health planning, and improving social, economic and quality-of-life outcomes. Indeed, it is usually the case that no single institution, and in many cases no single country, has sufficient data to provide results that can be applied broadly to clinical and translational research. However, the fragmentation and heterogeneity of the registries, which are often the result of spontaneous initiatives, limit the general applicability of their observations. METHODS: An inquiry has been carried out by the EPIRARE, a European Union (EU)-funded project ('Building Consensus and Synergies for the EU Registration of Rare Disease Patients') aiming at paving the way to the creation of a European Platform for RD Registries, by means of an on-line questionnaire among European RD registries on their main activities and needs, the way they deal with methodological, technical and regulatory issues and the way they find resources to carry on their activities. RESULTS: In spite of the heterogeneity of the European registries, some elements of relevance for an action to improve the situation of patient registries in the EU are apparent. The needs more frequently indicated by registry holders were financial support, motivation of data providers, data quality assessment, improvement of communication and visibility, and extension of collaborations. Moreover, the registry holders were in favor of a common EU platform providing services for RD registries. CONCLUSION: It appears that the current situation of the European registries provides the transition towards a more uniform, higher quality and better coordinated approach.

A model for the European platform for rare disease registries.

BACKGROUND: The current situation of rare disease (RD) registries is rather heterogeneous, and new ways to support the registration of RD patients are being sought in the European Union (EU) and the US. The project 'Building Consensus and Synergies for the EU Registration of RD Patients', funded by the EU, aimed to define a model platform for EU RD registries. METHODS: A number of surveys and extensive consultations among registry stakeholders have been carried out to study how the platform can best fulfill their needs. RESULTS: This web-based, multidisease and multipurpose platform is intended to provide a number of functions: a metadata and data repository function supporting the planning of research studies and the production of predefined outputs for the funding organizations and the public, provision of tools and resources of use to registries, promotion of registration and networking among patients and professionals. CONCLUSION: Its main impact is expected to be on data and procedures standardization, on the establishment of new registries, on the sustainability of the smaller ones, and on the registration of those RDs for which a dedicated registry is not sustainable, e.g. ultra-rare diseases or diseases for which there is no special research, clinical or economic interest. It will also impact on the production of sounder information on RD and RD-dedicated health systems, by promoting registry data comparability and quality.

Informed consent in clinical research in France: assessment and factors associated with therapeutic misconception.

BACKGROUND: Informed consent in clinical research is mandated throughout the world. Both patient subjects and investigators are required to understand and accept the distinction between research and treatment. AIM: To document the extent and to identify factors associated with therapeutic misconception in a population of patient subjects or parent proxies recruited from a variety of multicentre trials (parent studies). PATIENTS AND METHODS: The study comprised two phases: the development of a questionnaire to assess the quality of informed consent and a survey of patient subjects based on this questionnaire. RESULTS: A total of 303 patient subjects or parent proxies were contacted and 279 questionnaires were analysed. The median age was 49.5 years, sex ratio was 1 and 61% of respondents were professionally active. Overall memorisation of the oral or written communication of informed consent was good (69-97%), and satisfaction with the process was around 70%. Therapeutic misconception was present in 70% of respondents, who expected to receive better care and ignored the consequence of randomisation and treatment comparisons. This was positively associated with the acuteness and severity of the disease. CONCLUSION: The authors suggest that the risk of therapeutic misconception be specifically addressed in consent forms as an educational tool for both patients and investigators.

From compulsory to voluntary immunisation: Italy's National Vaccination Plan (2005-7) and the ethical and organisational challenges facing public health policy-makers across Europe.

Increasing geographical mobility and international travel augment the ease and speed by which infectious diseases can spread across large distances. It is therefore incumbent upon each state to ensure that immunisation programmes are effective and that herd immunity is achieved. Across Europe, a range of immunisation policies exist: compulsion, the offer of financial incentives to parents or healthcare professionals, social and professional pressure, or simply the dissemination of clear information and advice. Until recently, immunisation against particular communicable diseases was compulsory in Italy. The Italian National Vaccination Plan (NVP) (2005-7) paved the way for regions to suspend the sanctions associated with compulsory vaccinations for children when certain criteria are met--for example when immunisation coverage is high and when effective monitoring/surveillance systems are in place--and thus marked a milestone in the move from compulsory to voluntary immunisation. The forthcoming NVP for 2008-10 confirms the liberal approach to vaccination in Italy as it entrusts to the regions responsibility for the achievement and maintenance of herd immunity. This paper reviews the arguments for and against compulsory and voluntary immunisation in relation to the Italian NVP (2005-7) and in the context of the diverse immunisation policies that exist across Europe. It concludes with cautious support for the NVP and an associated shift from compulsory to voluntary immunisation in Italy, and draws similarities between issues concerning regional variation in immunisation policy in Italy and national variation in immunisation policy across Europe and beyond.