Xenotransplantation from the ethical viewpoint. An outline]

The duty to save and to preserve lives on one hand, and the scarcity of human donor organs on the other hand call for a search for new organ sources, including xenogenic ones. Xenotransplantation, however, is not only in need of medical research, but also of ethical analysis. The latter is not to be considered a substitute for moral intuition, but rather a foundation of it by way of a critical evaluation of the ethical principles and reasons involved. This basically demands an analysis of the legitimacy of the aims and of the acceptability of the means for xenotransplantation. It includes safeguarding informed consent; risk assessment and the protection of not only the recipient, but also others; the question of limitation of personal rights; allocation problems; and last but not least animal protection. The aim is to clarify the ethical status of xenotransplantation in general and the question of a moratorium regarding clinical trials due to unsolved problems of infectivity and immunosuppression in particular by way of an integrative approach to both scientific developments and ethical analysis.     

Executive summary

Abstract:  The International Xenotransplantation Association islet xenotransplantation consensus statement describes the conditions for undertaking clinical trials of porcine islet products in type 1 diabetes. Chapter 1 reviews the key ethical requirements and progress toward the definition of an international regulatory framework for clinical trials of xenotransplantation. Chapters 2 to 7 provide in depth and agreed-upon recommendations on source pigs, pig islet product manufacturing and release testing, preclinical efficacy and complication data required to justify a clinical trial, strategies to prevent transmission of porcine endogenous retrovirus, patient selection for clinical trials, and informed consent. It is planned to update this initial consensus statement in a year's time in light of progress in research, changes in the regulatory framework, and comments submitted after publication.     

The challenge of informed consent for increased risk living donation and transplantation

The Organ Procurement and Transplantation Network (OPTN) mandates that organ recipients provide "specific informed consent" before accepting organs that the OPTN defines as "increased risk". However, the OPTN does not provide specific guidelines for what information should be disclosed to potential recipients. Such vagueness opens the door to inadequate informed consent. This paper examines the ethical dimensions of informed consent when the prospective living donor has self-reported behaviors associated with increased risk for infection transmission. Donor privacy is a primary ethical concern that conflicts with recipients' informed consent for use of increased risk organs. We propose that both the increased risk status and the specific behavior be disclosed to the recipient. Because the actual risk posed is linked to the type of risk behavior, disclosure is therefore needed to make an informed decision. The donor's risk behavior is material to recipients' decision making because it may impact the donor-recipient relationship. This relationship is the foundation of the donation and acceptance transaction, and thus comprises a critical feature of the recipient's informed consent. Optimizing a recipient's informed consent is essential to protecting patient safety and autonomy.     

Informed Consent for Living Donation: A Review of Key Empirical Studies,Ethical Challenges and Future Research

Given the organ scarcity, live organ donation is increasingly considered a viable alternative for kidney and liver transplantation. Yet living donation challenges the ethical principle of nonmaleficence by subjecting healthy individuals to medical, psychosocial and unknown risks. Therefore, transplant providers, policy‐makers and donors are committed to ensuring that prospective donors provide adequate informed consent to undergo the procedure. Informed consent for living donation is ethically required as a means of demonstrating respect for donor's autonomy and protecting their safety. However, all elements of informed consent are fraught with difficulties due to the unique nature of the donation process and outcome. This paper reviews empirical research on informed consent for live kidney donors (LKD) and live liver donors (LLD) for both adult and pediatric recipients. As this review shows, studies that empirically assessed the quality of informed consent elements reveal considerable variability and deficiencies across the informed consent process, suggesting the need for improvement. This review highlights challenges to each element of consent for both LKDs and LLDs, and situates trends within broader policy contexts, ethical debates and avenues for future innovative research.     

Ethical Issues With Informed Consent From Potential Living Kidney Donors

Living organ donation and participation in clinical research trials have several features in common from an ethical perspective. The primary similarity is risk justification: the risk of harm to living organ donors and clinical research participants is justified by a resulting benefit to one or more other individuals. Some authors hold that organ donation and clinical trial participation are full-fledged duties. Such an implicit likening of the two leads to several considerations regarding informed consent in each situation. Informed consent raises ethical concerns in every medical context, and some of those concerns, such as competence, understanding, autonomy, and free or voluntary choice, are uniquely relevant to living organ donation and clinical trial participation. Most countries regulate informed consent procedures for living organ donation in great detail, and although informed consent procedures for clinical trial participation are somewhat less detailed, their rules are subject to review by ethics committees. It would be constructive for research participation informed consent procedures and living organ donation informed consent procedures to learn from one another.     

Ethical aspects of informed consent in obstetric anesthesia--new challenges and solutions

Informed consent is a cornerstone and routine component of the ethical practice of modern medicine. Its full theoretical application to specific clinical situations, however, presents a number of ethical dilemmas for health care providers. Obstetric anesthesia, in particular, presents many unique challenges to the process of informed consent. In this review, the ethical background to the doctrine of informed consent within the context of “principlism” is explored and critiqued. The application of principlism to actual clinical situations, the limitations of principlism in the peculiarities of the patient-physician encounter, as well as possible alternative models of ethical discourse is discussed. The process of informed consent can be broken down into seven elements: Threshold elements or preconditions, which include 1) decision-making capacity or competency of the patient, 2) freedom or voluntariness in decision-making, including absence of over-riding legal or state interests; informational elements, including 3) adequate disclosure of material information, 4) recommendation, and 5) an understanding of the above; consent elements, which include 6) decision by the patient in favor of a plan and 7) authorization of that plan. Each of these elements is discussed in turn, and their implications, especially for the anesthesiologist and the obstetric patient, are addressed.     

Informed consent for facial transplantation

Now that partial face transplantation has been performed, attention is focused on likely functional, aesthetic and immunological outcomes, and full facial transplantation is the likely next step. Facial transplantation has been the source of ethical debate, a key part of which focuses on valid informed consent. We review the process of informed consent in health settings, assessing how applicable the current standards are for facial transplantation. The factors which need to be assessed during the screening programme are outlined. We conclude that both individual and process factors are important in obtaining consent for radical new procedures, and outline our own gold standard for ensuring informed consent in facial transplantation.     

Ethics and regulation in organ procurement research

This article explores the role of ethics and regulation in human research conducted by organ procurement agencies; basic ethical principles for human research are outlined. Organ procurement agencies are not required to observe federal regulations; however, voluntary adherence will ensure that procurement research is conducted according to current standards of ethical practice. Although most organ procurement research will qualify for exempt status, this determination should be made by an institutional review board. Even if studies qualify for exempt status, there is a moral presumption that informed consent should be sought, unless certain narrow conditions for waiver of consent are satisfied. Finally, when future research utilizing organ procurement records is anticipated, procurement coordinators should provide sufficiently detailed information to families about such plans to permit their advance informed consent to research activities.     

Ethical issues in pediatric orthopaedics

The orthopaedist who treats children confronts the usual ethical issues of educating patients, obtaining informed consent, and making choices among unproven outcomes. When dealing with children, the issue of informed consent is confounded because the person giving the consent is not the person who will bear the consequences of the treatment. When the patient is a teenager, the issues of education, consent, and treatment decisions require patience, tact, and perseverance by the physician.     

Ethical issues surrounding high-risk kidney recipients: implications for the living donor

Evaulating patients for living kidney donor transplantation involving a recipient with significant medical issues can create an ethical debate about whether to proceed with surgery. Donors must be informed of the surgical risk to proceed with donating a kidney and their decision must be a voluntary one. A detailed informed consent should be obtained from high-risk living kidney donor transplant recipients as well as donors and family members after the high perioperative risk potential has been explained to them. In addition, family members need to be informed of and acknowledge that a living kidney donor transplant recipient with pretransplant extrarenal morbidity has a higher risk of a serious adverse outcome event such as graft failure or recipient death. We review 2 cases involving living kidney donor transplant recipients with significant comorbidity and discuss ethical considerations, donor risk, and the need for an extended informed consent.     

An investigation into the obtainment of informed consent for HIV-tests in psychiatric patients]

AIDS confronts the psychiatrist with the dilemma of stress resulting from a positive test result on the one hand and the responsibility of preventing the spread of the disease on the other hand. Psychiatric disturbances sometimes limit a patient's ability to give informed consent, which is an ethical precondition to testing. The legal standards of informed consent are discussed. During the 6-month period after the first HIV-positive test at Weskoppies Hospital, a further 48 patients were tested; 42 were examined to test the obtaining of informed consent. Diagnoses, reasons for testing and results were noted. Comprehension of the nature of the illness and the implications of the test were examined in a structured clinical interview. The nature of consent and the feedback of the result to the patient were examined. Results indicate that the psychiatric disturbance is a poor indication of the ability to give informed consent. The latter should be evaluated separately. If informed consent cannot be obtained, the patient should be treated as positive until accountability has been restored. Written consent offers the patient the opportunity to assimilate written information and contributes to informed consent. AIDS remains a problem of education and the feedback of seronegativity will help to curb future high-risk behaviour.     

Informed consent: is it always necessary?

Informed consent plays a pivotal role in human clinical research. It serves as a marker for the subject's comprehension of all the pertinent elements of the study. It is also a pledge by the investigator that during the trial, the rights and safety of the subject will be protected. Informed consent attempts to ensure that ethical behaviour will be upheld throughout the study. However, obtaining informed consent from certain vulnerable populations is a challenge, and thus warrants improvement. While informed consent is mandated for almost all clinical trial involving human subjects, there are situations of emergency research and trials with minimal risk that call for a waiver of the consent.     

Disclosure of individual surgeon's performance rates during informed consent: ethical and epistemological considerations

OBJECTIVE: The purpose of the paper is to examine the ethical arguments for and against disclosing surgeon-specific performance rates to patients during informed consent, and to examine the challenges that generating and using performance rates entail. METHODS: Ethical, legal, and statistical theory is explored to approach the question of whether, when, and how surgeons should disclosure their personal performance rates to patients. The main ethical question addressed is what type of information surgeons owe their patients during informed consent. This question comprises 3 related, ethically relevant considerations that are explored in detail: 1) Does surgeon-specific performance information enhance patient decision-making? 2) Do patients want this type of information? 3) How do the potential benefits of disclosure balance against the risks? RESULTS: Calculating individual performance measures requires tradeoffs and involves inherent uncertainty. There is a lack of evidence regarding whether patients want this information, whether it facilitates their decision-making for surgery, and how it is best communicated to them. Disclosure of personal performance rates during informed consent has the potential benefits of enhancing patient autonomy, improving patient decision-making, and improving quality of care. The major risks of disclosure include inaccurate and misleading performance rates, avoidance of high-risk cases, unjust damage to surgeon's reputations, and jeopardized patient trust. CONCLUSION: At this time, we think that, for most conditions, surgical procedures, and outcomes, the accuracy of surgeon- and patient-specific performance rates is illusory, obviating the ethical obligation to communicate them as part of the informed consent process. Nonetheless, the surgical profession has the duty to develop information systems that allow for performance to be evaluated to a high degree of accuracy. In the meantime, patients should be informed of the quantity of procedures their surgeons have performed, providing an idea of the surgeon's experience and qualitative idea of potential risk.     

Voluntary informed consent and good clinical practice for clinical research in South Africa: ethical and legal perspectives

Most differences, shortcomings and contradictions regarding voluntary informed consent for participation in clinical research relate to the South African-specific guidance documents, i.e. South African Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa (2006) and Ethics in Health Research: Principles, Structures and Processes (2004). These documents do not fulfil all the ethical and legal requirements for voluntary informed consent for clinical research participation in South Africa. International guidance documents reflect the minimum of the ethical requirements for the conduct of clinical research. Country-specific documents should be updated and aligned with relevant legislative and legal principles of that jurisdiction to ensure that research participants are adequately protected. The South African-specific guidance documents therefore require revision to address these deficiencies.     

Elements for Adequate Informed Consent in the Surgical Context

Given a history of atrocities and violations of ethical principles, several documents and regulations have been issued by a wide variety of organizations. They aim at ensuring that health care and clinical research adhere to defined ethical principles. A fundamental component was devised to ensure that the individual has been provided the necessary information to make an informed decision regarding health care or participation in clinical research. This article summarizes the history and regulations for informed consent and discusses suggested components for adequate consent forms for daily clinical practice in surgery as well as clinical research.     

Ensuring the Availability of Specimens for Research

Abstract: The need to ensure the availability of breast cancer specimens for research was identified by the National Action Plan on Breast Cancer (NAPBC) as a top priority. In September 1994 the National Cancer Institute (NCI)/NIH held a conference to assess the specimen needs and to make recommendations to the Biological Resources Working Group of the NAPBC. One recommendation was that informed consent should be obtained routinely at the time of tissue access to allow for research use of the tissue specimens in the future. An ethical issues subcommittee was formed to develop a model informed consent document. The subcommittee included patient advocates, ethicists, lawyers, pathologists, clinicians, and laboratory researchers. A set of basic principles to guide the collection, storage, and distribution of human specimens was designed to protect patient confidentiality while enabling biomedical research. The model informed consent was developed to be used in the context of the guiding principles. After addressing numerous ethical and legal issues, the draft consent was translated for low literacy and tested in focus groups. Comments from the focus groups led to the development of a fact sheet about use of tissue in research and a shortened consent form. The model consent form has been widely distributed. Several issues remain to be resolved, and these are discussed. Changes in institutional forms and procedures will likely be required since the consent form is intended for use in the routine care setting. The model consent form and/or its derivatives and the process of administering it should be field tested to determine where problems may arise. To ensure that specimens will be available for critical research efforts in the future, we will need to assure patients that benefits outweigh risks in this type of research.     

Ethical considerations in anaesthesia journals

It has been shown that instructions to authors in nonanaesthesia biomedical journals often fail to require authors to state that the study was approved by an ethics committee and informed consent obtained from participants; articles also often omit mentioning these points. We examined 11 English-language journals, which are listed in the 'Anesthesiology' category of 1995 SCI Journal Citation Reports, to see whether the instructions to authors of anaesthesia journals mention the following ethical factors: approval of the study by an ethics committee, informed consent, redundant publication, fraud, authorship, conflict of interest and protection of patients' privacy. We also examined 673 articles which appeared in these anaesthesia journals ( July to December issues of 1996) to see whether they stated acquirement of ethics committee approval and informed consent. All journals addressed the avoidance of redundant publications and unjustifiable authorship. Ten journals required approval of studies and signatures from all authors, eight journals mentioned informed consent. Only seven required the disclosure of any conflict of interest and the protection of patients' privacy. More than 90% of the articles stated that the study was approved and informed consent obtained.     

Bioethical interpretation of intensive care]

The bioethical interpretation concerns both those receiving intensive care (IC) and the nature of the treatment itself. The principle of autonomy expressed in the doctor-patient relationship is achieved through the use of informed consent and may also be used in the unique context of patients in IC. Organ-function replacement treatment raises the ethical question of the definition and management of the limit to treatment. The appropriateness of IC can be defined by clinical and ethical criteria and aims to avoid inappropriately excessive treatment. In order to improve the decision-making process involving bioethical questions, the authors outline a number of working approaches: the use of informed consent even in IC, the possible role of Advanced Directives in IC, epidemiological studies, operator training.     

Ethics of Frey syndrome: Ensuring that consent is truly informed

Frey syndrome is a widely recognized sequela of parotidectomy with a variable prevalence dependent upon diagnostic criteria. There exists a multitude of strategies for both prevention and treatment. Surgeons are obligated to engage patients in a frank and open discussion of the operative risks, benefits, and alternatives. Due to uncertainty regarding the significance of Frey syndrome postoperatively, the process of informed consent and preoperative decision‐making pose a potential ethical quandary. This commentary is designed to heighten the awareness of the preoperative informed consent process by dissecting the ethical tenets underlying these patient encounters using Frey syndrome as an example, ensuring that patients are granted the opportunity to participate in their own care in accordance with the concept of individual autonomy. © 2010 Wiley Periodicals, Inc. Head Neck, 2010     

Ethical and regulatory challenges associated with the exception from informed consent requirements for emergency research: from experimental design to institutional review board approval

Clinical research studies conducted in emergency settings under the waiver of consent provision outlined in federal regulations are uncommon, yet the importance of such research that may result in potentially lifesaving interventions is indisputable. Surgeons, as well as health care professionals in other disciplines of medicine, should be aware of the multiple challenges facing them if they contemplate conducting a research trial without the prospective informed consent of enrolled subjects. The challenges associated with conducting research studies using the exception from informed consent requirements for emergency research are numerous, beginning with ensuring an appropriate study design, understanding state and federal regulations that govern such emergency research studies, and continuing through a complicated and sometimes arduous institutional review board (IRB) process that is unique to these studies. This article will describe the challenges encountered when implementing the exception from informed consent requirements for emergency research and will provide surgeon researchers with an understanding of the ethical controversies surrounding such studies.