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.

Preemptive kidney transplantation: an ethical challenge for organ allocation policies.

Preemptive transplants are advisable in advanced stages of kidney disease. The clinical advantages of preemptive transplantation over dialysis are evident. Nevertheless, preemptive transplantations raise ethical concerns, particularly regarding the allocation of medical resources. The present article proposes some criteria for organ allocation policies regarding preemptive transplantations: criteria regarding medical benefit and justice are absolutely essential when addressing the issue of organ allocation, but other ethical values should also be taken into account. The "principle of double effect" offers useful pointers.

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.

Is an opt-out organ donation system desirable? Comments on a new law.

A law that introduces an opt-out system for organ donation has recently come into force in Wales. The debate surrounding the effectiveness and ethical acceptability of an opt-out system continues, though the available data have still not provided definitive proof that an opt-out system is more efficient than an opt-in system. Systems based on implied consent but with specific safeguards would appear more suitable and more respectful of ethical principles than those based on a more aggressive form of presumed consent.

Organ Allocation Policies 10 Years After UNESCO's Universal Declaration on Bioethics and Human Rights.

BACKGROUND: October 19, 2015, marked the 10th anniversary of the adoption by the General Conference of the United Nations Educational, Scientific and Cultural Organisation (UNESCO) of the "Universal Declaration on Bioethics and Human Rights," which was signed by representatives of the 191 member states of the conference. The declaration is of major importance: it was the first legally binding document approved by a global organization to address the whole range of subjects covered by bioethics. RESULTS: Among the principles laid down in the declaration, those most relevant for the allocation of organs are benefit and harm (Article 4), equality, justice and equity (Article 10), nondiscrimination and nonstigmatization (Article 11), solidarity and cooperation (Article 13), social responsibility and health (including access to quality health care; Article 14), and sharing of benefits (Article 15). CONCLUSIONS: Policies concerning the allocation of organs cannot disregard the principles affirmed in the Declaration.

Facial transplants: current situation and ethical issues.

The first transplantation of a face from a cadaver was performed in 2005, since when about thirty have been performed globally. The technique is now beginning to appear in Italy. Face transplants are performed exclusively on persons who have suffered devastating lesions to the face. The ethical problems involved are very considerable, particularly where personal identity is concerned. The case records reveal surprisingly positive outcomes regarding both clinical follow-up and functional recovery, as well as psychological aspects and social integration. Thus, while early documents addressing the ethical issues involved in facial transplants were somewhat cautious or even unfavourable on the subject of this technique, a positive approach is now more prevalent.

Some ethical implications of "adaptive" trials.

Adaptive trials are a new type of sequential trial, as yet not very widespread, in which each step can be modified on the basis of findings from the preceding step. In other words, the data accumulated during the study are used to modify the trial design. The potential of this type of trial is highly promising, especially for the development of therapies for rare diseases. The planning, conduct and management of data from adaptive trials are extremely complex processes and call for highly specialised skills. Without going into the merits of the experimental protocols, the aim of this article is to point out some ethical aspects that call for caution, as well as the need for ethics committees to be aware of the challenges posed by these trials.

Information to be given to patients: a UK judgment marks a turning point.

A recent judgment by the Supreme Court of the United Kingdom marks a turning point in the way doctors should inform patients of the risks associated with clinical treatment. The Courts previously based their judgments on the so-called "Bolam test", according to which a physician's conduct would be considered acceptable if it would be supported by a responsible body of medical opinion. The new ruling overturns this approach: doctors should no longer ask themselves what is their colleagues' prevailing stance and conform to it, but should instead assess the circumstances from the point of view of the particular patient in each case.

Organ Allocation Policies According to EU National Bioethics Committees: A Comparison.

The opinions expressed by European National Bioethics Committees (NBCs) on organ transplants were examined. Very few opinions specifically addressed the issue of allocation, and those that did revealed not only conflicts between clinical criteria and ethical principles but also potential competition between ethical principles that are equally important and deserving of respect. An examination of the various opinions showed agreement on the need to balance conflicting criteria and principles, as well as the diversity of the available practical options. Although NBCs agree that the choice of allocation policies should focus on therapeutic criteria while also considering other parameters, such as justice, clinical usefulness, and waiting period, the relative weights to be attributed to each vary among committees.

On the "pendulum" of bioethics.

According to a well-known philosopher, the life of ethics was saved, at the beginning of the 1970s, by medicine. The claim is based on the consideration that the questions then being posed by medicine were actual and dramatic, forcing ethicists and philosophers to abandon their mostly useless abstract speculations. Since the early years of the new century some authors have been harsh in their criticism of bioethics, accusing it not only of not "returning the favour" to medicine but also of seriously hindering medical practice and, above all, research, by subjecting them to unnecessary constraints. Some of the more restrictive and bureaucratic regulations have been relaxed over the years, to the extent that some authors suggest that the bioethics pendulum "is taking a swing to the permissive". There are nonetheless some fundamental principles and values that do not admit of concessions. Provided these are properly guaranteed, it is appropriate to simplify overly rigid regulations (such as those concerning consent to the use of health data) and allow research to achieve potentially useful results.

On akrasia and the "prevention paradox".

The term akrasia describes the behaviour of persons who knowingly and consciously act against their better judgement and is exemplified by various unhealthy lifestyle choices. Prevention should aim to provide guidance in the choice of lifestyle. While at the individual level this is best directed towards those who are at high risk, at a general population level it is preferable to target the higher numbers of individuals at low risk rather than the fewer high-risk subjects. This is the so-called "prevention paradox". From an ethical viewpoint it is important, when planning measures to maximise the benefits for the community, not to neglect individual subjects: the common good is created by promoting and making the most of the good of the individual.

A new tool in the global fight against the traffic in human organs.

The Council of Europe (CoE) Convention against Trafficking in Human Organs is a significant tool in the global fight against the traffic in human organs for transplantation. It is addressed to all states throughout the world, not only to CoE member states. The Convention binds states to adopt reciprocally consistent and co-ordinated measures to establish organ trafficking as a criminal offence. The legal fundamentals and co-ordinated action envisaged in the Convention provide practical support in the implementation of principles already sanctioned in previous declarations.

In defence of non-remunerated blood donation.

Numerous documents concerning bioethics and human rights recognise that the human body and its parts should not be bought or sold or be source of profit. Voluntary, non-remunerated donation is recognised by all the major competent bodies in the field as a cornerstone for the safe and sustainable supply of blood and blood products. In several nations so-called "donors" nonetheless receive remuneration or reimbursements that frequently verge on actual payments. In addition, there is constant pressure - especially from for-profit organisations--to introduce payments for "donors". Against this background it may perhaps be useful to reassert the basic principles underlying the non-remunerated donation of blood.

On the tenth anniversary of the "Universal Declaration on Bioethics and Human Rights".

In 2005 the representatives of 191 states meeting for the General Conference of UNESCO unanimously approved the "Universal Declaration on Bioethics and Human Rights". The Declaration is the only instrument of its kind: it was the first document adopted by a global organisation that addressed the whole range of issues with which bioethics is concerned and that is a legal instrument. Many of the principles affirmed in the Declaration had already been amply absorbed into the discipline of bioethics. All of them can be traced to the dignity and equality of every individual. The most evident novelty is to be found less in the content of the principles than in the balancing of individual and societal perspectives. Also in evidence are several compromises that were adopted in order to promote dialogue and mutual understanding.

From the Law of European Delegation to the Legislative Decree on experiments with animals: consequences for biomedical research.

The provisions contained in the Legislative Decree no.26 signed by Italy's President on 4th March 2014 will have a considerable impact on the future of experiments with animals. The article briefly describes the stages of the decree's complicated passage through Parliament and the resulting text, which includes bans on: the use of animals for xenotransplants or research on drugs of abuse; the breeding of dogs, cats and non-human primates for experimental use; research without anaesthetic or analgesics that causes pain to the animal, except when anaesthetics or analgesics are being investigated. There is widespread feeling in the scientific community that these provisions will hinder the advancement of biomedical research in Italy.

Helsinki 50 years on.

Ever since its adoption the Declaration of Helsinki has been universally recognised as a key landmark in the ethics of medical research involving human subjects. Over fifty years it has been revised seven times and supplemented twice with explanatory notes. The debate surrounding its contents and organisation continues unabated and becomes particularly lively every time the text is reviewed. One of the most controversial issues is recourse to the placebo: the conditions laid down for its use are held by many to offer insufficient guarantees for the protection of those receiving it.

Some considerations on integrity in scientific research.

Some aspects of research integrity are presented and discussed, primarily through reference to institutional documents, particularly those published by the European Union. A scrupulous approach to scientific publications is emphasized as being crucial to integrity in research, while clinical trials are indicated as an area in which especially strict rules should be observed. The article comprises: an introduction, in which "integrity in research" is defined; some examples of violations of research integrity; an analysis of possible ways to implement general rules in particular contexts; a call for scrupulousness in scientific publications as a crucial factor in research integrity; a brief reference to ethics in clinical trials, where the observation of particularly severe rules is imperative.

Regulatory policies in paediatric research: how harmonised are the ethical principles?

Trials involving children generate considerable practical problems of a mainly ethical nature. While there is wide-ranging agreement on the basic ethical requisites for these trials, substantial--and even profound--differences remain between national and international regulatory policies. For the European Union Directive 2001/20/EC is the basic reference for national regulations regarding clinical trials. Article 4 of this Directive deals with trials on minors. The present article compares the regulations of this Article with four other documents regulating paediatric trials in Europe, the US and Japan. This comparison points to different approaches relating particularly to: risk acceptability, risk/benefit assessments, informed consent, assent of minors.

Living organ donations: a comparison between the positions of national bioethics committees.

Numerous documents have been published by the national bioethics committees of the European Union and Council of Europe member countries on the subject of organ transplantation. The present paper examines those that address the question of living donation with a focus on kidney grafts. Although it is not possible to ensure absolute completeness since not all the documents produced over the years are accessible and English translations are often lacking, this review covered evaluations of the most significant ones. There has been a preponderance of attention to the issue of informed consent, while the issue of donor risk has been addressed only summarily, if at all.