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One of the founding principles of research ethics is that subjects should be treated equally. In the words of the Belmont Report, “equals ought to be treated equally.” This principle does not imply that all subjects should be treated exactly the same. Rather, subjects who are similar in relevant respects should receive similar treatment. Clinical status is clearly relevant to determining how subjects should be treated. Greater resources should be devoted to subjects who have worse diseases. In contrast, fame is irrelevant. Subjects should not receive greater resources simply because they are famous. A more challenging question, one that pervades clinical research yet has received almost no attention in the literature, is whether subjects' level of scientific importance is relevant to determining how much support they should receive..

Background Many published accounts of clinical trials report no differences between the treatment arms, while being underpowered to find differences. This study determined how the authors of these reports interpreted their findings. Study Design We examined 54 reports of surgical trials chosen randomly from a database of 110 influential trials conducted in 2008. Seven that reported having adequate statistical power (β ≥ 0.9) were excluded from further analysis, as were the 32 that reported significant differences between the treatment arms. We examined the remaining 15 to see whether the authors interpreted their negative findings appropriately. Appropriate interpretations discussed the lack of power and/or called for larger studies. Results Three of the 7 trials that did not report an a priori power calculation offered inappropriate interpretations, as did 3 of the 8 trials that reported an a priori power Conclusions Negative findings in underpowered trials were often interpreted as showing the equivalence of the treatment arms with no discussion of the issue of being underpowered. This may lead clinicians to accept new treatments that have not been validated.

Background If trials of therapeutic interventions are to serve society9s interests, they must be of high methodological quality and must satisfy moral commitments to human subjects. The authors set out to develop a clinical-trials compendium in which standards for the ethical treatment of human subjects are integrated with standards for research methods. Methods The authors rank-ordered the world9s nations and chose the 31 with >700 active trials as of 24 July 2008. Governmental and other authoritative entities of the 31 countries were searched, and 1004 English-language documents containing ethical and/or methodological standards for clinical trials were identified. The authors extracted standards from 144 of those: 50 designated as ‘core’, 39 addressing trials of invasive procedures and a 5% sample (N=55) of the remainder. As the integrating framework for the standards we developed a coherent taxonomy encompassing all elements of a trial9s stages. Findings Review of the 144 documents yielded nearly 15 000 discrete standards. After duplicates were removed, 5903 substantive standards remained, distributed in the taxonomy as follows: initiation, 1401 standards, 8 divisions; design, 1869 standards, 16 divisions; conduct, 1473 standards, 8 divisions; analysing and reporting results, 997 standards, four divisions; and post-trial standards, 168 standards, 5 divisions. Conclusions The overwhelming number of source documents and standards uncovered in this study was not anticipated beforehand and confirms the extraordinary complexity of the clinical trials enterprise. This taxonomy of multinational ethical and methodological standards may help trialists and overseers improve the quality of clinical trials, particularly given the globalisation of clinical research.

Recent federal regulations allow for emergency research without prospective consent provided that additional protections for the subjects are provided. One of these is community consultation.To determine how to feasibly consult the community and what to do with the findings.In connection with an ongoing study of l-arginine for brain injury at a public hospital's trauma center, we consulted three sets of community representatives using different methods. To sample the entire population of the county, we conducted a random-digit dialing survey (456 residents). To sample individuals served by the hospital, we interviewed a convenience sample of 566 patients and individuals in the waiting area. To sample particularly interested individuals, we conducted a series of public meetings (114 participants). In each case, the same instrument was used to ascertain their attitudes toward the study in general and toward its major features (randomization, waiver of consent, location, risks/benefits). To control for framing effects, items were randomly presented in a positive or negative fashion.All methods proved feasible, but telephone surveys were most efficient and guaranteed the desired demography. Even for a very low-risk study, only 79.75% of respondents would be willing to participate. The rate of approval for the major features was lower, with only 67.78% approving of the risk/benefit ratio, 53.7% approving of randomization, 57.66% approving of the consent waiver, and 44.45% approving of the location. The most significant factors affecting the rate of approval were the method of consultation and the framing of items (both p.001), age, ethnicity, and previous research participation (all p.01).Community consultation is feasible, but its results depend heavily on method of consultation, framing of questions, and choice of community. It may well demonstrate unexpectedly substantial opposition. There needs to be a better definition of the process and a better understanding of how to respond to its results.

Pharmacogenetics offers the prospect of an era of safer and more effective drugs, as well as more individualized use of drug therapies. Before the benefits of pharmacogenetics can be realized, the ethical issues that arise in research and clinical application of pharmacogenetic technologies must be addressed. The ethical issues raised by pharmacogenetics can be addressed under six headings: (1) regulatory oversight, (2) confidentiality and privacy, (3) informed consent, (4) availability of drugs, (5) access, and (6) clinicians' changing responsibilities in the era of pharmacogenetic medicine. We analyze each of these categories of ethical issues and provide policy approaches for addressing them.

BACKGROUND: Conflicts of interest pose a threat to the integrity of scientific research. The current regulations of the U.S. Public Health Service and the National Science Foundation require that medical schools and other research institutions report the existence of conflicts of interest to the funding agency but allow the institutions to manage conflicts internally. The regulations do not specify how to do so. METHODS: We surveyed all medical schools (127) and other research institutions (170) that received more than $5 million in total grants annually from the National Institutes of Health or the National Science Foundation; 48 journals in basic science and clinical medicine; and 17 federal agencies in order to analyze their policies on conflicts of interest. RESULTS: Of the 297 institutions, 250 (84 percent) responded by March 2000, as did 47 of the 48 journals and 16 of the 17 federal agencies. Fifteen of the 250 institutions (6 percent)--5 medical schools and 10 other research institutions--reported that they had no policy on conflicts of interest. Among the institutions that had policies, there was marked variation in the definition and management of conflicts. Ninety-one percent had policies that adhered to the federal threshold for disclosure ($10,000 in annual income or equity in a relevant company or 5 percent ownership), and 9 percent had policies that exceeded the federal guidelines. Only 8 percent had policies requiring disclosure to funding agencies, only 7 percent had such policies regarding journals, and only 1 percent had policies requiring the disclosure of information to the relevant institutional review boards or to research subjects. Twenty journals (43 percent) reported that they had policies requiring disclosure of conflicts of interest. Only four federal agencies had policies that explicitly addressed conflicts of interest in extramural research, and all but one of the agencies relied primarily on institutional discretion. CONCLUSIONS: There is substantial variation among policies on conflicts of interest at medical schools and other research institutions. This variation, combined with the fact that many scientific journals and funding agencies do not require disclosure of conflicts of interest, suggests that the current standards may not be adequate to maintain a high level of scientific integrity.

This paper presents a standard for assessing the validity of placebo-controlled trials in circumstances in which such trials might be unjustly denying appropriate therapies to members of the control group. This standard categorizes the types of risks that can or cannot be imposed upon consenting research subjects in such control groups. The paper also shows how needed research can be conducted while respecting the proposed ethical standard. Both the problem and the proposed standard are illustrated by reference to the major trials of the thrombolytic agents.

Men who pursue active treatment for metastatic prostate cancer face a choice between medical or surgical castration. While both alternatives have documented side-effects (e.g. loss of libido, breast enlargement and tenderness, hot flashes, and nausea), their psychosocial impacts are not well understood. As part of a study of patients' treatment decision making, we have sought to construct a patient-based measure of the salient disease and treatment-related qualities of life experienced by these men subsequent to treatment. Focus groups (15 with patients, two with wives) were used to develop candidate Likert scale questionnaire items representing quality of life issues that patients said were important. These items were combined with assessments of symptoms, comorbidity, and generic measures of functional status and well-being in a mail survey of patients treated at the Houston VAMC and two other Houston hospitals (n = 201, response rate = 63%). Psychometric analyses (principal components and multitrait scaling) were used to identify distinct dimensions of life quality; correlations with generic measures, and symptom reports were used in validation analyses. Qualitative analyses of focus group data identified three major domains of life quality: self-perceptions, anxiety about the effects of treatment, and concern with the process of decision making and treatment. Psychometric analyses identified nine reliable and valid indicators of prostate cancer-related quality of life: body image, sexual problems, spouse affection, spouse worry, masculinity, cancer-related self-image, cancer distress, cancer acceptance, and regret of treatment decision. Internal consistency (alpha) ranged form 0.71 to 0.90. Correlations with reference scales (e.g. MOS Mental Health Index, Profile of Mood States) and symptom status supported concurrent validity. Prostate cancer patients perceive a number of important psychosocial consequences of their treatment. These consequences are represented by nine scales comprising a brief (35 items) disease and treatment sensitive health-related quality of life instrument, which we will use in monitoring the outcomes of patients' treatment choices.

This paper distinguishes four major types of futility (physiological, imminent demise, lethal condition, and qualitative) that have been advocated in the literature either in a patient dependent or a patient independent fashion. It proposes five criteria (precision, prospective, social acceptability, significant number, and non-agreement) that any definition of futility must satisfy if it is to serve as the basis for unilaterally limiting futile care. It then argues that none of the definitions that have been advocated meet the criteria, primarily because their proponents have not paid sufficient attention to the problematic nature of the data supporting the use of their definitions.

Unlike medications, the dissemination of surgical procedures into practice is not regulated. Before marketing, pharmaceutical products are required to be shown safe and efficacious in comparative clinical trials which utilize bias-reducing strategies designed to reduce the distortion of estimates of treatment effect by predispositions towards the investigational intervention or control. Unless an investigational device is involved, the corresponding process for surgical innovations is usually unregulated and therefore may not be based upon adequate evidence. Given these differences, we sought to evaluate the state of clinical research on invasive procedures. We conducted a systematic review of publications from 1999–2008 that reported the results of studies evaluating the effects of invasive therapeutic procedures, focusing on trials which appeared to influence practice. Our objective was to determine what proportion of studies evaluating surgical procedures use a comparative clinical trial design and methods to control bias. This paper reports our results and raises concerns about the methodological, and therefore the ethical, quality of clinical research used to justify the implementation of surgical procedures into practice.

There has been a growing concern over establishing norms that ensure the ethically acceptable and scientifically sound conduct of clinical trials. Among the leading norms internationally are the World Medical Association's Declaration of Helsinki, guidelines by the Council for International Organizations of Medical Sciences (CIOMS), the International Conference on Harmonization's standards for industry (ICH), and the CONSORT group's reporting norms (Consolidated Standards of Reporting Trials), in addition to the influential U.S. Federal Common Rule, Food and Drug Administration's (FDA) body of regulations, and information sheets by the Department of Health and Human Services. There are also many norms published at more local levels by official agencies and professional groups.Any account of international standards should cover both scientific and ethical norms at once – the two are conceptually intertwined. Recent sources recognize that “[s]cientifically unsound research on human subjects is unethical in that it exposes research subjects to risks without possible benefit.”

The emergence of the human immunodeficiency virus (HIV) as a serious public health threat has rekindled long dormant debate about individual physicians' duty to treat potentially contagious patients. Because of the widely accepted common-law tenet of the "no duty [to treat] rule," previous work on a duty to treat focused on historical reviews, medical society position statements, and the ethical arguments upon which the statements are based. The passage of the Americans with Disabilities Act has rendered these discussions moot by creating, through federal civil rights mechanisms, a legal duty to treat patients with HIV, enforceable under considerable penalties. The paper also concludes that there has been inadequate attention paid to similar civil rights concerns of infected physicians.

Can a medical ethic be developed for a liberal state? This is the issue posed by the authors of both of the works under review. Brennan in Just Doctoring thinks that the answer is yes and that his theory of just doctoring provides just such an ethic. Emanuel in The Ends of Human Life thinks that the answer is no and that an adequate resolution of the dilemmas of medical ethics requires an alternative political philosophy, liberal commun itarianism.

This paper focuses on invasive therapeutic procedures, defined as procedures requiring the introduction of hands, instruments, or devices into the body via incisions or punctures of the skin or mucous membranes performed with the intent of changing the natural history of a human disease or condition for the better. Ethical and methodological concerns have been expressed about studies designed to evaluate the effects of invasive therapeutic procedures. Can such studies meet the same standards demanded of those, for example, evaluating pharmaceutical agents? This paper describes a research project aimed at examining the interplay and sometimes apparent conflict between ethical standards for human research and standards for methodological rigor in trials of invasive procedures. The paper discusses how the authors plan to develop a set of consensus standards that, if met, would result in substantial and much-needed improvements in the methodological and ethical quality of such trials.

This study examines the intravenous use of two thrombolytic agents [streptokinase (SK) and tissue plasminogen activator (tPA)] in the acute phase of myocardial infarction (MI). These two agents have very different costs and offer an excellent opportunity to study both the impact of economic factors on clinical decisionmaking and the potential for cost savings by limiting the use of expensive new therapeutic agents. A nationwide survey of the 5,792 acute care general hospitals listed in the American Hospital Association's 1988 data file was responded to by 2,651 hospitals (46%) and revealed that 2,384 of these responding hospitals (90%) were using thrombolytic therapy. For 2,200 of these 2,384 hospitals (92%), the respondent was a physician who primarily used one of the two drugs. Eight hundred eighty-six of these 2,200 physicians (40%) primarily used SK while 1,314 (60%) primarily used tPA. SK users were more concentrated in federal public hospitals (69% used SK) than in nonfederal public hospitals (47% used SK), and were least concentrated in private hospitals (36% used SK). There was no difference between the rate of SK vs tPA use in investor-owned and not-for-profit private hospitals. SK users most often (62%) cited various economic factors as the reason for their choice. The users of tPA primarily (73%) cited clinical preferability as the reason for their choice even though trials are still ongoing to see which drug is preferable. Several multivariate analyses shed light upon the association between choice of thrombolytic agent and various additional physician and hospital characteristics. These data clearly indicate that while new therapies are rapidly implemented by the medical community, considerations of cost have a substantial impact upon the pattern of implementation and reflect a desire to implement cost savings in the use of new drugs.

Background Innovative approaches are needed to allow for research in the emergency setting while not compromising either the rights or the interests of the subjects enrolled in such research. The emergency consent exception was developed to meet this need. Purpose The goal was to describe the timing of initial contact with relatives and the timing of obtaining informed consent for a research study in patients with severe traumatic brain injury. Methods The study was designed as a prospective, observational study of 129 patients enrolled in an emergency study of traumatic brain injury conducted under the emergency consent exception. Detailed descriptive information was collected both about the availability of relatives of patients enrolled in a study of traumatic brain injury to give prospective consent within the time period required for entering the study and about the extent to which they did give prospective consent during that time period. Results The number of patients with relatives who could be contacted by research staff increased with time after injury, with 3% (95% CI=0 to 6%), 25% (95% CI=18 to 32%), and 43% (95% CI=35 to 52%) having family at 1, 3, and 6 h, respectively postinjury. An additional 15% were available within the next 6 h. The median time after injury to the initial family contact by the research staff was 2.0 h for patients who had relatives already present at the hospital and 5.7 h for patients whose family had already been contacted by the hospital. The percentage of family members actually giving prospective research consent was much smaller; only 18% actually gave prospective consent within 6 h postinjury. The proportion of critically ill patients with family available to give prospective consent for enrollment in emergency research studies depends primarily on the time period allowed for enrollment in the individual study and the length of the transition from initial contact to completed prospective consent. Limitations The study was performed in a specific patient population and may not be generalizable to other settings. Conclusions Careful attention should be paid by investigators and IRBs as to whether the emergency consent exception is really required for a particular study, or whether the study could proceed using only prospective consent with a longer recruitment period, more research sites, and a higher yield of available family members giving prospective consent. Measures that could shorten the time between initial contact and obtaining informed consent (for example, allowing consent over the phone rather than requiring written consent) might decrease the need for the emergency consent exception. Clinical Trials 2007; 4: 631—637. http://ctj.sagepub.com

The European patent system allows for the introduction of moral issues into decisions about the granting of patents. This feature has greatly impacted European debates about the patenting of biotechnology. This essay explores the European experience, in both the European Union and the European Patent Organization. It argues that there has been great confusion surrounding these issues primarily because the Europeans have not developed a general theory about when exclusion from patentability is the best social mechanism for dealing with morally offensive technologies.

Substantial progress has been made in developing treatments that reduce the risk of fractures in osteoporosis. However, available treatments are only partially effective, they are not widely used, and there is need to search for more effective means of fracture prevention. Currently known effective means of reducing fractures were found using randomized placebo-controlled trials. The use of placebo controls in clinical trials has been a subject of significant controversy in recent years. The Declaration of Helsinki revision of October 2000 caused great concern among clinical investigators about the future use of placebo controls if known effective therapeutic agents are available. A working group of ethicists, clinical trial design experts, and clinical investigators examined the current state of knowledge of osteoporosis treatment and trials. They concluded that if placebo controls put subjects at substantial risk of serious outcomes, they are not ethically permissible. Placebo controls in osteoporosis trials with fracture as the measured outcome are permissible only under narrowly defined conditions. Placebo controls may be used if competent, well-informed patients refuse approved therapies for sound reasons, there is a reasonable basis for substantial disagreement or lack of consensus among professionals about whether approved treatments are better than placebos, or subjects are refractory to known effective agents. Active control trials are permissible and desirable if they can be designed and conducted in ways that overcome the interpretive difficulties often associated with such trials.

Pharmacogenetics--the effect of genotype on drug response--holds the promise of safer and more effective drug therapy. Genetic tests would be routinely given to patients prior to prescription of a drug, with therapeutic decisions based on the patient's drug-response profile. This paper examines the operational changes and the ethical, legal, and policy challenges that pharmacogenetic medicine poses for key actors in the health care system. Adaptation by drug companies, regulatory agencies, physicians, patients, insurers, and public funding agencies will be necessary to integrate pharmacogenetic medicine into health care.

Some attention is beginning to be paid in the recent literature of bioethics and health policy to a variety of ethical issues that arise in the business aspects of the practice of medicine. These include such questions as advertising in medicine, physician self-referral, physician fees, and conflicts of interest in clinical trials. These questions arise primarily, but not exclusively, in those settings in which physicians practice fee-for-service medicine, and there are many such settings in the United States and elsewhere. I want to suggest that the controversies surrounding these issues result from neither society in general nor physicians in particular having decided which of two models of the physician is the more appropriate model, and that progress in resolving these issues requires an unequivocal adoption of one of them. In the first section of this article, I will present an outline of these two models. In the next two sections

In recent years, bioethics has increasingly become an international area of inquiry with major contributions being made not only in North America but also in Europe and in the Pacific Rim countries. This general observation is particularly true for research ethics. Little attention has been paid, however, to this internationalization of bioethics in general and research ethics in particular, and there are few studies comparing what has emerged in the different countries.

The recent medical literature in the United States has contained an extensive discussion of the issue of medical futility. Inspired by cases such as that of Helen Wanglie (Angell, 1991), in which the husband of an elderly woman in a persistent vegetative state demanded continued life-prolonging interventions, clinicians and ethicists have debated whether or not patients are entitled to receive life prolonging interventions (demanded by them or the surrogates who speak for them) even when the clinicians judge those interventions to be futile. Some (Blackhall, 1987) have emphasized the objectivity of the clinical judgements that the interventions in question are futile, and have permitted physicians in such cases to unilaterally decide to limit those futile interventions. Others (Youngner, 1988) have emphasized the value-laden nature of such judgements, and have insisted that it is the patient or the family who must decide which interventions will be provided.

Successful practice of cardiovascular medicine requires familiarity with the complex ethical issues that accompany therapeutic innovation and diffusion. Even as technologies transition from experimental to standard care, challenges remain. Mechanical circulatory support devices, for instance, are increasingly conceptualized as conventional therapies. Despite this, or perhaps because of it, the ethical issues surrounding the use of these devices in patients with end-stage organ dysfunction are becoming increasingly apparent. In this paper, we provide an introduction to ethical considerations related to the use of ventricular assist devices (VADs) in end-stage organ failure, focusing on three stages or decision points: initiation, continued use, and deactivation. Our goal is not to exhaustively resolve these dilemmas but to illustrate how ethical considerations relate to decision making.

OBJECTIVES: To estimate resource consumption and the extent of futile care among patients admitted to the pediatric intensive care unit (PICU). STUDY DESIGN: A prospective cohort study of 353 consecutive admissions followed for 1334 patient-days during the PICU stay at the Texas Children's Hospital in Houston, Texas. Participants were 353 children and adolescents who were hospitalized in the PICU during September and October 1993. Three broad operational definitions of futility were developed to capture the maximum extent of resource consumption related to medical futility. Definition 1 (imminent demise futility) was developed by an objective, validated, severity of illness measure (Pediatric Risk of Mortality Score) to identify patients with high mortality risks. Definition 2 (lethal condition futility) was used to identify patients in the PICU whose long-term survival was unlikely. Definition 3 (qualitative futility) was used to identify patients with high morbidity. Resource consumption was measured according to the number of patient-days in the PICU and the Therapeutic Intervention Scoring System. RESULTS: Twenty-three (6.5%) patients representing 36 (2.7%) patient-days met at least one of the definitions of medical futility for some of the days when they were in the PICU. None of the patient-days that met any of the definitions of medical futility were associated with high resource consumption compared with non-futile care patient-days. CONCLUSIONS: Despite our use of broad definitions of medical futility, relatively small amounts of resources were used in futile PICU care. This suggests that attempts to reduce resource consumption in the PICU by focusing on medical futility are unlikely to be successful. (J PEDIATR 1996;128:742-7)

Objective: To study the perceptions of outcome and the diffusion into practice of innovative approaches such as palliative surgery and heart transplantation to treat hypoplastic left heart syndrome. Design: A forced-choice questionnaire was sent to 108 US neonatology section heads. Responses were analyzed using Wilcoxon matched pairs, χ2analysis, and multivariant logistic regression. Results: Ninety-three questionnaires (86%) were returned. All respondents discussed palliative surgery or transplantation or both with parents; 71 (76%) of 93 also discussed comfort care. Nineteen (24%) of 80 recommended comfort care only, 51 (64%) of 80 recommended surgery only, and 10 (12%) of 80 recommended both. Of the 61 respondents recommending one or both surgical procedures, palliative surgery was recommended by 44 and transplantation by 33. Respondents perceived that transplantation was associated with a lower 1-year mortality than palliative surgery (P Conclusions: Palliative surgery and transplantation are widely used to treat hypoplastic left heart syndrome. The continued availability of comfort care suggests that these surgical procedures are still in transition from experimental technology to standard of care. (Arch Pediatr Adolesc Med. 1996;150:487-490)

Over the last twenty years, considerable attention has been paid to ethical issues arising out of the provision of care in intensive care units (ICUs). This is not surprising. After all, so much of the literature of medical ethics is an attempt to evaluate the appropriateness of medical interventions (usually high-technology interventions) designed to prolong life when the effectiveness in terms of life-extension is uncertain, the resulting quality of the life prolonged is questionable, and the costs (economic and otherwise) of providing the intervention are high. This type of evaluation is particularly needed in intensive care units where, because of the severity of the patient’s illness, the outcomes are especially uncertain and questionable and the costs are extremely high.

MORAL PLURALISM IS A VALUABLE ASPECT OF A free society but sometimes creates conflicts in medical care when individual physicians object to providing certain legal but morally controversial services, such as abortion, physician-assisted suicide (where it is legal), and palliative sedation to unconsciousness. Genuine conscience-based refusals (CBRs) are refusals in which a physician believes that providing the requested service would violate his or her core moral beliefs (religious or secular), thereby causing personal moral harm. Conscience-based refusals should be a “shield” to protect individual physicians from being compelled to violate their core moral beliefs rather than a “sword” to force their beliefs onto patients. This partially explains why many physicians who invoke CBRs refer their patients to physicians willing to provide the requested care. Savulescu has characterized CBRs as self-serving acts accomplished at the expense of patients. Others accept CBRs as legitimate acts to protect moral integrity despite the potential negative consequences for patients. Both characterizations neglect a complexity: society may obtain higherquality medical care in aggregate by accommodating some CBRs. In this Commentary, CBRs are addressed from this societal perspective.

There is a growing interest in comparison of international health care data with the hope that such studies will enable individual systems to learn from other systems. Such comparisons, however, presuppose that there exist common criteria for evaluating health care systems. The main thesis of this paper is that these comparative studies are misleading because they employ inappropriate operationalizations of these criteria because the operationalizations are based upon mistaken global conceptualizations of the criteria in question. The essay provides a methodological critique of what has been done and sets a new agenda for future research.

Empirical research can aid ethical reflection in bioethics by identifying issues, by seeing how they are currently resolved, and by assessing the consequences of these current resolutions. This potential can be misused when the ethical issues in question are fundamentally non-consequentialist or when they are consequentialist but the empirical research fails to address the important consequences. An example of the former problem is some recent studies about bad consequences resulting from commercialized living kidney donor programs. These consequences could be avoided, but the crucial non-consequentialist ethical issues about exploitation and commercialization would still remain. Examples of the latter problem are provided by recent studies of the allocation of ICU beds and of physician deception, where important consequences were not adequately studied.

OBJECTIVE To review the use of Natural Death Act declarations (living will procedures) in pediatric patients. The implementation of such declarations for children is now possible in six states, including Texas, by specific statutory provisions. DESIGN Retrospective study. SETTING Pediatric ICU in a university hospital. PATIENTS Records of patients who had a Texas Natural Death Act declaration, either discussed and signed or discussed only, were studied. Patients who had another vehicle of limiting care (e.g., a do-not-resuscitate order) were excluded from the study. MEASUREMENTS AND MAIN RESULTS Reviewed characteristics included age, primary diagnosis, and concurrent complications. Also examined were who raised the issue of limiting care (parent or physician), the initial reaction of the other party, what support was withdrawn, what support was added, the final outcome (including the time from implementing limited care to death), and the description of witnesses. Discussions were held with parents of 17 patients, and 13 Natural Death Act declarations were actually implemented. In all but three instances, the patient died within 4 hrs from the time support was withdrawn. The main supports that were withdrawn were ventilators and catecholamines. In half of the cases, morphine sulfate was added for anticipated pain relief and sedation. All decisions were reached by close consultation between the family and the physicians, with the physicians raising the issue in 11 of the 17 cases and the family raising the issue in six cases. In 15 of the 17 patients, consultation with the Bioethics Committee was not necessary. The majority of difficulties involved resolving issues that beset patients with HIV infections, and finding appropriate witnesses as prescribed by the statute. CONCLUSIONS We conclude that the Natural Death Act works well in situations involving dying children and their parents.

In recent years, one of the crucial concepts often invoked in policy debates about the provision of health care is the concept of the right to health care. Some have argued that health care is a privilege and not a right. Others, probably the more prevalent group, insist that there is a right to health care and that it has significant implications for the ways in which health care is provided and for the level of governmental funding of health care for the indigent. Regardless of the position being advocated, there are few serious discussions of the organization and financing of health care that fail to invoke, either explicitly or implicitly, the right to health care.

Objectives. To describe the medical follow-up ordered, the health care utilization, the appointment compliance, and the risk factors associated with noncompliance in patients who are discharged after a pediatric intensive care unit (PICU) stay.Methods. A prospective, analytic, cohort study of 111 critically ill children, age 1 day to 16 years, who were admitted to a 30-bed PICU in an urban, tertiary-care, pediatric teaching hospital compared children who were compliant with medical follow-up with those who were not. The main outcomes measured were emergent and unscheduled physician visits during the first 6 weeks after hospital discharge; compliance with ordered medical follow-up after hospital discharge; and comparisons of socioeconomic, demographic, and medical need factors between compliant and noncompliant children.Discharge orders for follow-up appointments with general pediatricians and subspecialists were collected from the chart at hospital discharge. Patients were contacted after hospital discharge to determine whether and when they received medical follow-up; 28% were found to be noncompliant. Risk factors associated with noncompliance were evaluated. Emergent and unscheduled physician visits were tracked during the first 6 weeks after hospital discharge.Results.Lack of follow-up orders at hospital discharge did not affect the frequency of emergent visits. Children fell into 2 groups: those who were 100% compliant and those with ≤67% compliance. No socioeconomic or demographic risk factors could be identified between the 2 groups. Compared with the 100% compliant patients, patients who were compliant with ≤67% of appointments were more severely ill, as defined by higher peak pediatric risk of mortality scores during their PICU stay (11.5 vs 8.4), longer PICU length of stays (10.1 days vs 4.6 days), and longer hospital length of stays (25.5 days vs 14 days). Most predictive of noncompliance was the number of medical appointments ordered by physicians. Patients with 3 or more appointments were less likely to be compliant with follow-up. After hospital discharge, children were more likely to visit a primary care physician compared with a subspecialist (95% vs 82%). When patients were ordered to see a specialist, scheduled appointments were much better attended than the recommended appointments (92% vs 67%).Conclusions. Lack of ordered medical follow-up did not affect emergent visits. In this group of critically ill children, a significant percentage (28%) did not receive timely medical follow-up. No socioeconomic or demographic risk factors were identified in noncompliant children. However, severity of illness (higher peak pediatric risk of mortality score, longer PICU stay, and longer hospital stay) and the number of follow-up appointments ordered were predictors of noncompliance. Potential exists for implementing strategies to improve compliance in identified populations.

Background and Objectives.When innovative, not yet fully proven therapies are introduced, physicians may have neither experience nor sufficient data in the medical literature to assist in their decision to discuss them with and/or recommend them to patients. Little is known about how physicians deal with this uncertainty. Moreover, when multiple physicians caring for a single patient have reached different conclusions regarding this new therapy, the potential for disagreement exists that could give rise to ethical issues as well as cause confusion to the patient. To explore these topics, we investigated the attitudes of specialists to therapies for two life-threatening diseases: hypoplastic left heart syndrome (HLHS) and short bowel syndrome.Methods.A forced choice questionnaire was distributed to the heads of neonatology, pediatric cardiology, and pediatric gastroenterology training programs asking about their outcome impressions and treatment recommendations and about the local availability of treatments. In addition, responses from specialists from the same institution were linked in a confidential manner to evaluate the frequency of disagreement within the same institution. Responses were analyzed using χ2 and Wilcoxon matched pair analysis as appropriate.Results.The overall rate of response was 79%. In institutions that had both neonatology and pediatric gastroenterology training programs, there was a 59% response rate compared with a 73% response rate from institutions that had both neonatology and cardiology programs. Significant differences were noted among specialists as to who would be involved in discussions of therapeutic options with patients in both HLHS and short bowel syndrome. Differences also were noted in the willingness of specialists to discuss and recommend therapies, in the perceived survival and quality of life by various specialists after transplant and palliative surgery, and in the local availability of various options. The neonatologists and gastroenterologists at the same institution disagreed on responses in 34% of the questions with only 1 of the 25 pairs in full agreement. In contrast, the neonatologists and pediatric cardiologists at the same institution disagreed in only 14% of the questions with 7 of the 28 pairs in full agreement.Conclusions.Substantial disagreement among specialists about new interventions was found. There seem to be fewer differences among specialists when dealing with the more mature therapy, HLHS. Two major ethical issues arise. First, there seems to be no accepted professional standard to which individuals can appeal when determining whether to discuss or recommend new, not-yet-fully-proven technologies. Second, there is the potential for much patient confusion when counseling physicians recommend different options. Colleagues as individuals and specialists as groups should talk to each other before individual discussions with families to ensure that there is a clear understanding of differing beliefs.

In the management of short gut, alternatives to long term total parenteral nutrition (TPN) exist, ranging from enteral feeding only to interventional, surgical management such as gut transplant or gut lengthening procedures. To understand attitudes and practice concerning short gut management, a survey was sent in the spring of 1997 to the directors of 102 Neonatology (Neo) and 47 Gastroenterology (GI) fellowship programs with 70% and 85% response respectively. Chi square with Yates correction and Wilcoxon matched paired analysis are used as appropriate.

In Reply. —We are pleased that Drs Bauman and Vawter support the general direction of the Houston policy and that their groups are in the process of developing similar policies. We agree with Bauman that society as a whole needs to address the issues of resource allocation and rationing. However, that does not free institutions from their duty as responsible stewards of the resources made available to them, to consider the allocation of those resources as they decide whether providing demanded interventions is appropriate. Institutional integrity, we have argued, demands that this be considered. We also believe, in disagreement with Bauman, that a failure to provide the intervention unless the patient ultimately agrees is not abandonment. It must be remembered that all appropriate care would, according to step 7 of our protocol, continue to be provided, and abandonment is only the failure to provide appropriate care. A failure to provide inappropriate care

AN INFANT born with multiple congenital abnormalities that rendered survival unprecedented required high-dose vasopressors to maintain blood pressure. After several days, gangrene developed in the extremities, and the parents sequentially demanded amputations of several limbs in an attempt to "do everything." The surrogate decision maker for a comatose woman dying of multisystem organ failure in an intensive care unit (ICU) was her estranged husband; they separated because of repeated spousal abuse. Despite many conferences with the husband recommending comfort measures and a do-not-resuscitate order, the husband demanded that the medical staff "do everything to my wife." A public hospital serving an indigent community of several hundred thousand had a full ICU, and 3 patients were being kept in the emergency department on ventilators. One of the patients in the ICU was a gentleman who had been ventilator dependent and unresponsive for 41/2 months after a cardiac arrest; his daughter insisted

Background: It is widely assumed that "futile" treatment consumes significant health care resources. This is a prospective cohort study. Setting: The setting was the medical intensive care unit of Ben Taub General Hospital, a large public hospital in Houston, Tex. Objective: To assess the frequency of intensive care unit patients meeting any of three broad definitions of futility. Subjects: Subjects consisted of 129 consecutive patients admitted to the study intensive care unit during a 6-week period in the fall of 1993. Main Outcome Measures: Operational definitions for three types of futility described in the literature were developed:Imminent demise futility, death imminent regardless of intervention, was assessed by using the APACHE II (Acute Physiology and Chronic Health Evaluation II) scoring system to determine the likelihood of mortality at more than the 90%, 95%, and 99% probabilities.Lethal condition futility, conditions incompatible with long-term survival, included five separate disease processes.Qualitative futility, conditions with an unacceptable quality of life, was assessed as a persistent vegetative state or as meeting criteria for poor prognosis due to a hypoxic ischemic coma. Results: Only 2 bed-days (0.3%) were used by patients with more than 90% predicted mortality; 22 bed-days (3.6%) were used by patients with poor prognosis due to hypoxic ischemic coma; and 101 bed-days (16.4%) were used by patients satisfying criteria for the five lethal conditions. Conclusions: The frequency of futile interventions appears to be low unless one is willing to accept a definition that includes patients who could survive for many months. If confirmed in other settings, this suggests that concepts of futility will not play a major role in cost containment. (Arch Intern Med. 1996;156:100-104)

Objective. —To assess pairwise differences between placebo, unopposed estrogen, and each of three estrogen/progestin regimens on selected heart disease risk factors in healthy postmenopausal women. Design. —A 3-year, multicenter, randomized, double-blind, placebo-controlled trial. Participants. —A total of 875 healthy postmenopausal women aged 45 to 64 years who had no known contraindication to hormone therapy. Intervention. —Participants were randomly assigned in equal numbers to the following groups: (1) placebo; (2) conjugated equine estrogen (CEE), 0.625 mg/d; (3) CEE, 0.625 mg/d plus cyclic medroxyprogesterone acetate (MPA), 10 mg/d for 12 d/mo; (4) CEE, 0.625 mg/d plus consecutive MPA, 2.5 mg/d; or (5) CEE, 0.625 mg/d plus cyclic micronized progesterone (MP), 200 mg/d for 12 d/mo. Primary Endpoints. —Four endpoints were chosen to represent four biological systems related to the risk of cardiovascular disease: (1) high-density lipoprotein cholesterol (HDL-C), (2) systolic blood pressure, (3) serum insulin, and (4) fibrinogen. Analysis. —Analyses presented are by intention to treat. P values for primary endpoints are adjusted for multiple comparisons; 95% confidence intervals around estimated effects were calculated without this adjustment. Results. —Mean changes in HDL-C segregated treatment regimens into three statistically distinct groups: (1) placebo (decrease of 0.03 mmol/L [1.2 mg/dL]); (2) MPA regimens (increases of 0.03 to 0.04 mmol/L [1.2 to 1.6 mg/dL]); and (3) CEE with cyclic MP (increase of 0.11 mmol/L [4.1 mg/dL]) and CEE alone (increase of 0.14 mmol/L [5.6 mg/dL]). Active treatments decreased mean low-density lipoprotein cholesterol (0.37 to 0.46 mmol/L [14.5 to 17.7 mg/dL]) and increased mean triglyceride (0.13 to 0.15 mmol/L [11.4 to 13.7 mg/dL]) compared with placebo. Placebo was associated with a significantly greater increase in mean fibrinogen than any active treatment (0.10 g/L compared with -0.02 to 0.06 g/L); differences among active treatments were not significant. Systolic blood pressure increased and postchallenge insulin levels decreased during the trial, but neither varied significantly by treatment assignment. Compared with other active treatments, unopposed estrogen was associated with a significantly increased risk of adenomatous or atypical hyperplasia (34% vs 1%) and of hysterectomy (6% vs 1%). No other adverse effect differed by treatment assignment or hysterectomy status. Conclusions. —Estrogen alone or in combination with a progestin improves lipoproteins and lowers fibrinogen levels without detectable effects on postchallenge insulin or blood pressure. Unopposed estrogen is the optimal regimen for elevation of HDL-C, but the high rate of endometrial hyperplasia restricts use to women without a uterus. In women with a uterus, CEE with cyclic MP has the most favorable effect on HDL-C and no excess risk of endometrial hyperplasia. ( JAMA . 1995;273:199-208)

Background: In 1991, Medicare began covering screening mammograms subject to copayment and deductible. This study evaluated the effectiveness of Medicare in removing financial barriers to screening mammography among low-income older women. Methods: In an inner-city public hospital's General Medicine Clinic, 119 consecutive, eligible, and consenting Medicare-enrolled women without known risk factors for breast cancer other than age, and no mammogram in the previous 2 years, were entered into a randomized controlled trial with follow-up after 2 months. The mean age was 71 years; 77% were black, 92% had an annual income below $10 000, and 52% had had a previous mammogram. All patients were counseled concerning indications for screening mammograms and Medicare coverage, and all were referred to a low-cost mammography facility. Sixty-one subjects were randomly assigned a voucher for a free screening mammogram at the referral facility. Obtaining a mammogram within 60 days of study entry was the main outcome measure. Results: Of the women given vouchers, 27 (44%) obtained screening mammograms, compared with six (10%) of those without vouchers ( P Conclusion: In a low-income, inner-city population of older women, financial barriers to screening mammography persist despite Medicare coverage. (Arch Intern Med. 1994;154:1217-1224)