Organ procurement after cardiocirculatory death: a critical analysis

To shorten the transplantation waiting time in the United States, federal regulations have been introduced requiring hospitals to develop policies for organ donation after cardiac (or circulatory) death (DCD). The practice of DCD is invoked based on the validity of the University of Pittsburgh Medical Center (UPMC) protocol and relies on the accuracy of the University of Wisconsin (UW) evaluation tool to appropriately identify organ donors. There is little evidence to support the position that the criteria for organ procurement adopted from the UPMC protocol complies with the dead donor rule. A high false-positive rate of the UW evaluation tool can expose many dying patients to unnecessary perimortem interventions because of donation failure. The medications and/or interventions for the sole purpose of maintaining organ viability can have unintended negative consequences on the timing and quality of end-of-life care offered to organ donors. It is essential to address and manage the evolving conflict between optimal end-of-life care and the necessary sacrifices for the procurement of transplantable organs from the terminally ill. The recipients of marginal organs recovered from DCD can also suffer higher mortality and morbidity than recipients of other types of donated organs. Finally, transparent disclosure to the public of the risks involved to both organ donors and recipients may contribute to open societal debate on the ethical acceptability of DCD.     

Balancing recruitment and protection: children as research subjects.

Since 1994, federal guidelines for research in the United States have called for the inclusion of special populations, among them, children, in clinical research (National Institutes of Health, 1998). While the guidelines are intended to assure the fair distribution of research benefits to children, this federal mandate has created an ethical dilemma for researchers. Health professionals involved in research with children are called on to balance improving access and recruitment of children for clinical trials with the need to protect this very vulnerable population. Given this balancing act, it is important for nurse-researchers to be familiar with the issues of informed consent and assent with children. Our article reviews instances of exploitation of children in research, laws and federal regulations on informed consent and assent designed to protect children, and research on factors that affect children's capacity to consent/assent. We conclude with recommendations to assure a proper balance between the need to recruit children into clinical trials and the need to protect their rights as human subjects.     

Evaluating the quality of information about alternatives to research participation in oncology consent forms

A careful consideration of the alternatives to research participation is an essential element of making an informed choice to enroll in a biomedical research study. While there is general agreement on the importance of informing prospective subjects about alternatives to research participation, little is known about how investigators communicate this information. The purpose of this study was to attempt to assess the quality of information about alternatives contained in informed consent documents in oncology randomized controlled trials. Our study indicates that there is room for improvement concerning the discussion of alternatives to research participation in informed consent documents in oncology randomized controlled trials. Though most of the documents in our study met the minimal disclosure standard found in the U.S. federal regulations, less than a third met the reasonable person standard, a widely accepted principle endorsed by the common law and various ethics guidelines and documents. There was a statistically significant difference between the alternative discussions in local and model forms (P < 0.0014). The alternatives discussions in local informed consent documents were more likely to receive higher scores than those in model consent documents, with an odds-ratio of 3.5 to 1.     

Legal regulation of human gene therapy

The adequacy of existing legal mechanisms to regulate clinical trials of human gene therapy is examined. Existing legal controls include the federal Guidelines for Research Involving Recombinant DNA Molecules and federal regulations for the protection of human subjects. Another significant mechanism is provided by judicial oversight, i.e., judicial decisions involving recombinant DNA research. Human gene therapy does raise new issues that still must be resolved. At least two weaknesses exist in the present regulatory system: first, Recombinant DNA Advisory Committee (RAC) only has authority over federally funded research, not work done with private support, and second, RAC is not mandated to focus on difficult ethical issues, e.g., germ-line therapy, that arise from human genetic engineering technology.     

关于活体器官供者的伦理思考

背景:活体器官伦理问题逐渐成为人们视野中的焦点和难点。目的:对活体器官供体伦理问题进一步研究。方法:应用计算机检索CNKI和VMIS数据库中2001-01/2011-05关于器官移植的文章,在标题和摘要中以"活体、供体"和"器官移植、伦理"为检索词进行检索。纳入与活体供体关联度高、本领域内的文献,主要选择权威杂志、核心期刊或者近期发表的文章。排除与此文目的无关的、内容和观点陈旧的及重复研究的文献。入选18篇文献和4本医学伦理学书籍进行综述。结果与结论:为了生命的健康续存,必须完善器官移植和捐献的法律法规,规范供体来源渠道,避免由于科技利益和经济利益的驱使任由活体供体买卖现象的存在空间,研究器官移植活体供体伦理问题,可促使人们提高活体供体捐赠积极性和主动性,解决器官移植供体短缺状况。     

关于活体器官供者的伦理思考

背景：活体器官伦理问题逐渐成为人们视野中的焦点和难点。目的：对活体器官供体伦理问题进一步研究。方法：应用计算机检索CNKI和VMIS数据库中2001-01/2011-05关于器官移植的文章,在标题和摘要中以＂活体、供体＂和＂器官移植、伦理＂为检索词进行检索。纳入与活体供体关联度高、本领域内的文献,主要选择权威杂志、核心期刊或者近期发表的文章。排除与此文目的无关的、内容和观点陈旧的及重复研究的文献。入选18篇文献和4本医学伦理学书籍进行综述。结果与结论：为了生命的健康续存,必须完善器官移植和捐献的法律法规,规范供体来源渠道,避免由于科技利益和经济利益的驱使任由活体供体买卖现象的存在空间,研究器官移植活体供体伦理问题,可促使人们提高活体供体捐赠积极性和主动性,解决器官移植供体短缺状况。     

Key concepts of clinical trials: a narrative review

The recent focus of federal funding on comparative effectiveness research underscores the importance of clinical trials in the practice of evidence-based medicine and health care reform. The impact of clinical trials not only extends to the individual patient by establishing a broader selection of effective therapies, but also to society as a whole by enhancing the value of health care provided. However, clinical trials also have the potential to pose unknown risks to their participants, and biased knowledge extracted from flawed clinical trials may lead to the inadvertent harm of patients. Although conducting a well-designed clinical trial may appear straightforward, it is founded on rigorous methodology and oversight governed by key ethical principles. In this review, we provide an overview of the ethical foundations of trial design, trial oversight, and the process of obtaining approval of a therapeutic, from its pre-clinical phase to post-marketing surveillance. This narrative review is based on a course in clinical trials developed by one of the authors (DJM), and is supplemented by a PubMed search predating January 2011 using the keywords "randomized controlled trial," "patient/clinical research," "ethics," "phase IV," "data and safety monitoring board," and "surrogate endpoint." With an understanding of the key principles in designing and implementing clinical trials, health care providers can partner with the pharmaceutical industry and regulatory bodies to effectively compare medical therapies and thereby meet one of the essential goals of health care reform.     

Current status and future of organ transplantation in Japan

When Organ Transplantation Law was issued, Japanese Organ Transplantation Network (JOT) was established. JOT plays a role in listing recipients, management and education of JOT coordinator(Co), publicity, and head-quarter at the time of organ donation. JOT Cos play roles in getting consent for organ donation from relatives, donor evaluation and management, organ transport, management of organ recovery and taking care of donor families during and after donation. Every prefecture has at least one own prefectural Co who is mainly working for public education and hospital development. They help JOT Co at the time of organ procurement. Most prefectures commission hospital staffs in procurement hospital to be an in-hospital Co, who find potential donors and support organ procurement.     

Ethical and legal aspects of the nursing records of organ donors for transplant

The objective of this study was to verify the ethical and legal aspects concerning the documentation of nursing practice in the organ donor's records. The records of the 12 organ donors admitted in a Brazilian University Hospital, from January/1992 to august/1996 were analysed. The donor consent was reported by nurses in 16.7% of the records. Defects that preclude legal value for the charting such as missing date or signature, erasure were found in 91.7% of the records.     

Parental Consent and Adolescent Risk Behavior Research

Purpose: To identify methodological issues related to the use of active or passive parental consent in school-based research on adolescent risk behavior research and to propose recommendations consistent with current legal and ethical standards in the United States.
Methods: Review and synthesis of the professional literature related to adolescents and parental consent, federal regulations and guidelines in the United States, and the author's experience presenting these arguments and issues to institutional review boards and funding agencies for over 10 years.
Findings: The procedures used for parental consent affect a study's participation rates, costs, and selection bias. When active parental consent is required, parental permission is typically obtained for only 30%–60% of students, compared to 93%–100% when passive consent is used. Extensive follow-up may result in 55%–100% of parents giving permission, but at significant cost (typically $20–$25 per student). Active consent results in the exclusion of minorities, students having problems in school, and students already engaged in or at risk for problem behaviors. Strong methodological reasons were identified for using passive parental consent procedures when possible. Current federal regulations include four areas for possible waiver or alterations in parental consent procedures, including the use of passive parental consent.
Conclusions: Health researchers must understand the methodological, legal, and ethical issues related to parental consent to produce high-quality, valid research about adolescents and to provide evidence for laws, policies, and regulations.     

Knowledge and beliefs of nurse researchers about informed consent principles and regulations

We examined differences in the knowledge and beliefs that exist among nurse researchers in the USA (n = 119) regarding informed consent and the use of data from patients' medical records. Using a mail survey, two domains of ethical knowledge and beliefs were assessed: the legal right to privacy and the moral right to privacy. More than half of the participants were very confident in their knowledge of institutional review board procedures, research ethics, informed consent, the legal right to privacy, and the moral right to privacy. In contrast, most rated themselves as uncertain about US federal research regulations and there was wide variation in knowledge about current federal guidelines. Those who were more confident in their knowledge of or had more practical experience with research ethics, were no more likely to answer correctly a question about current federal guidelines regulating the use of patient data from medical records than those who reported less confidence or experience.     

Identifying the potential organ donor: an audit of hospital deaths

Objective To quantify the potential for organ donation in Victoria and identify missed opportunities for organ donation.Design and setting Prospective medical record audit of all deaths in 12 Victorian hospitals.Measurements Data on deaths, total potential donors, organ donors and outcome of requests for organ donation were collected. Patients in whom brain death was confirmed or likely to occur and in whom organ donation was not requested (unrealised potential donors) were classified by an independent panel. Rates of organ donation and unrealised donors were determined as a proportion of total potential donors and hospital deaths and the maximal potential organ donor rate was estimated.Results Of 5551 deaths, there were 112 potential donors, with 66 requests for organ donation resulting in 39 consents (consent rate of 59%) and 37 organ donors (33% of total potential donors; 0.7% of hospital deaths). Two consented potential donors did not donate due to failed physiological support (5%). There were 46 medically suitable unrealised potential donors; 3 with confirmed brain death. Approximately half of these patients had treatment withdrawn in the intensive care unit and half in the Emergency Department. The estimated maximal potential donor rate was 30 per million population.Conclusions The potential for organ donation in Victoria is relatively low compared with previous estimates in Australia and overseas. An increase in the organ donation rate may be possible through increasing consent and the identification and support of potential donors. This would require substantial changes in clinical practice that have resource and ethical implications.     

Impact of informed consent requirements on cardiac arrest research in the United States: exception from consent or from research?

INTRODUCTION: Research in patients with life-threatening illness such as cardiac arrest is challenging since they can not consent. The Food and Drug Administration addressed research under emergency conditions by publishing new criteria for exception from informed consent in 1996. We systematically reviewed randomized trials over a 10-year period to assess the impact of these regulations. METHODS: Case-control study of published trials for cardiac arrest (cases) and atrial fibrillation (controls.) Studies were identified by using structured searches of MEDLINE and EMBASE from 1992 to 2002. Included were studies using random allocation in humans with cardiac arrest or atrial fibrillation prior to enrollment. Excluded were duplicate publications. Number of American trials, foreign trials and proportion of trials of American origin were compared by using regression analysis. Changes in cardiac arrest versus atrial fibrillation trials were calculated as risk differences. RESULTS: Of 4982 identified cardiac arrest studies, 57 (1.1%) were randomized trials. The number of American cardiac arrest trials decreased by 15% (95% CI: 8, 22%) annually (P = 0.05). The proportion of cardiac arrest trials of American origin decreased by 16% (95% CI: 10, 22%) annually (P = 0.006). Of 5596 identified atrial fibrillation studies, 197 trials (3.5%) were randomized trials. The risk difference between cardiac arrest versus atrial fibrillation trials being of American origin decreased significantly (annual difference -5.8% (95% CI: -10, -0.1%), P = 0.03). INTERPRETATION: Fewer American cardiac arrest trials were published during the last decade, when federal consent requirements changed. Regulatory requirements for clinical trials may inhibit improvements in care and threaten public health.     

Ethical issues in administrative continuous improvement. Applying the concept of prior notification to the conduct of firm trials

Consensus exists concerning the distinctions to be drawn between clinical practice and research. When the latter is undertaken, established regulations require that protocols including plans for obtaining subjects' informed consent be submitted to Institutional Review Boards for approval. Less consensus or codification exists concerning evaluations conducted by managers in health care settings. The recent development of firm systems, in which randomized, controlled designs are employed to evaluate administrative interventions, provides a unique context in which to consider whether the subjects of administrative evaluations should be afforded protections granted subjects of clinical research. Accordingly, the history of firm trials from an ethical perspective is reviewed. At the University of Washington, participants of such studies are informed through the process of prior notification, an adaptation of procedures employed widely to inform patients that records or specimens may be used in epidemiologic or biomedical research. Prior notification appears to be a useful refinement of the firm system methodology, one that may have application to managerial manipulations in other arenas.     

Implementing the Food and Drug Administration's Final Rule for Waiver of Informed Consent in Certain Emergency Research Circumstances

In 1996, the Food and Drug Administration released its Final Rule for Waiver of Informed Consent in Certain Emergency Research Circumstances (the Final Rule). The Department of Health and Human Services (DHHS) also released an update of its regulations related to waiver of informed consent in emergency research. These new regulations allow resuscitation research to proceed with a waiver of informed consent under very narrow and specific clinical research circumstances. Waiving informed consent for research participation has profound ethical and scientific implications. However, in unpredictable life-threatening clinical situations for which current therapy is unproven or unsatisfactory, patients usually are unable to consent on their own behalf to participate in clinical trials of potentially beneficial but experimental interventions. Because of the time-dependent nature of most resuscitation interventions, it is usually not feasible to identify and contact the legally authorized representative who can speak on behalf of the patient within the presumed therapeutic window of the intervention under investigation. For such clinical trials to proceed, a waiver of informed consent is usually necessary. Patients who are critically ill or injured and unable to provide meaningful prospective informed consent because of their current life-threatening condition are vulnerable and require additional protections beyond those for research subjects who can speak on their own behalf. The Final Rule and the DHHS-updated regulations incorporate a number of additional patient safeguards that must occur if a clinical trial is to proceed with waiver of informed consent. Specific means of adequately meeting these requirements are not described in the regulations. Although this was intentional on the part of the federal regulators so that individual protocols and research environments would direct the development of these patient safeguards, the lack of specific guidance has led to confusion on the appropriate implementation of the new regulations. This article reviews some of the key concepts of the Final Rule, with suggestions on their purpose and meaning. It also reviews the studies that have been approved to date to proceed with waiver of informed consent, and offers suggestions for the process of implementing the requirements of the Final Rule for research involving patients who are unable to give prospective informed consent.     

国际标准化脑死亡供肺获取1例

总结国际标准化脑死亡供体肺的获取经验，以形成一套适用于巾国临床肺移植的脑死亡供体获取标准和规范。本例脑死亡患者的判定严格按国际通用标准，项目负责人在确认家属捐献意愿后，组织2位以上的高年资神经内科、颅脑外科、麻醉科或ICU专家严格按“脑死亡判定标准”及“脑死亡判定技术规范”逐条认真检查患者。脑死亡判定成立后患者家属代表向医院方签署停止一切治疗的知情同意书，签署“脑死亡自愿无偿器官捐献申请书”。对机械通气50h的志愿捐献者进行脑死亡评估和供体器官功能评估后，严格按照国际标准化多脏器获取流程行供肺获取术。本例供体成功完成了肺的获取。实践证明这项操作流程规范可靠。     

Clinical management of the organ donor

Critical care nurses play a vital role in the clinical management of potential organ donors. Knowledge of the physiologic traits a donor will exhibit and the clinical interventions necessary to prevent circulatory collapse are essential in providing care to the organ donor. Maintaining hemodynamic stability in the donor optimizes organ function and improves the chances of successful results in transplant recipients.     

The human connection: the role of the nurse in organ donation

Organ transplantation has greatly improved the grim outlook of patients suffering from end-stage organ failure. Unfortunately, many of these waiting patients will not realize their dream of being transplanted since the number of organ donors referred to transplant programs simply does not meet the need. This article describes the role the nurse can play in organ donation by discussing medical criteria needed to assess the donor, the determination of neurologic death, and guidelines to approaching families for consent.     

Applying ethical guidelines in nursing research on people with mental illness

This article describes how ethical guidelines have been applied while interviewing psychiatric patients who were recovering from mental illness, especially from psychosis, to allow nurses to understand these patients' experiences. Because psychiatric patients are vulnerable, their participation in research involves ethical dilemmas, such as voluntary consent, legal capacity to consent, freedom of choice, and sufficient knowledge and comprehension. The first part of this article describes the most important ethical guidelines concerning human research. These have been published by different organizations, departments, committees and commissions for the purpose of protecting human rights and dignity whenever research participants are vulnerable persons or their capacity to consent is limited. At present, however, no special regulations govern research involving adults who have been diagnosed with a condition characterized by mental impairment. Furthermore, a relatively small body of research has documented the effects of various disorders (e.g. psychiatric conditions) on decision-making capacity per se. One basic moral and policy question is whether these individuals should ever be involved in research. The second part of this article concentrates on how the investigator made sure that participating patients had understood their role in this particular piece of nursing research. During the interviews the investigator noticed that some ethical dilemmas required further study and debate because of the lack of consensus on the proposed regulatory provisions on research involving institutionalized persons and their ability to make an informed and voluntary decision.     

Limitations of clinical trials in acute lung injury and acute respiratory distress syndrome

PURPOSE OF REVIEW: To review the challenges and limitations of randomized clinical trials in acute respiratory distress syndrome, with special emphasis on those pertaining to ventilatory management. RECENT FINDINGS: Superbly executed randomized trials of ventilatory strategy have garnered deserved attention from the critical care community and yet have illustrated the limitations of our current approach to clinical research in this area. Inexact definitions, incomplete mechanistic understanding of complex pathophysiology, inappropriate outcome variables, diverse therapeutic environments, lengthy data acquisition time and ethical constraints on trial design limit the applicability of randomized control trial methodology to acute respiratory distress syndrome and acute lung injury. As yet, clinical practice does not seem to have been greatly impacted by the implications of completed randomized controlled trials per se. Recent issues, both ethical and interpretive, regarding control group participants have raised troubling and theoretically important issues that are yet to be fully resolved. SUMMARY: Without tighter definitions of the condition under treatment, more specific targets for interventions to act upon, stratification that recognizes key interactive elements, and cointerventions based on better mechanistic understanding, randomized controlled trials of new drugs, ventilatory strategy, and other management approaches in acute respiratory distress syndrome are likely to remain a blunt instrument for investigation. As valuable as they are for calling important therapeutic principles to attention and for helping to suggest general guidelines for care, the limitations of randomized controlled trials for treating the individual with acute respiratory distress syndrome must be acknowledged.