Search

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.

Human clinical research has become a huge economic enterprise (Morin et al. 2002; Noah 2002). Because the human subject at the center can be so easily marginalized, many commentators recommend spec...

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

A fundamental assumption of utility-based analyses is that patient utilities for health states can be measured on an equal-interval scale. This assumption, however, has not been widely examined. The objective of this study was to assess whether the rating scale (RS), standard gamble (SG), and time trade-off (TTO) utility elicitation methods function as equal-interval level scales. We wrote descriptions of eight prostate-cancer-related health states. In interviews with patients who had newly diagnosed, advanced prostate cancer, utilities for the health states were elicited using the RS, SG, and TTO methods. At the time of the study, 77 initial and 73 follow-up interviews had. been conducted with a consecutive sample of 77 participants. Using a Rasch model, the boundaries (Thurstone Thresholds) between four equal score sub-ranges of the raw utilities were mapped onto an equal-interval logit scale. The distance between adjacent thresholds in logit units was calculated to determine whether the raw utilities were equal-interval. None of the utility scales functioned as interval-level scales in our sample. Therefore, since interval-level estimates are assumed in utility-based analyses, doubt is raised regarding the validity of findings from previous analyses based on these scales. Our findings need to be replicated in other contexts, and the practical impact of non-interval measurement on utility-based analyses should be explored. If cost-effectiveness analyses are not found to be robust to violations of the assumption that utilities are interval, serious doubt will be cast upon findings from utility-based analyses and upon the wisdom of expending millions in research dollars on utility-based studies.

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.

Clinical sites have in their databases the names of many patients with specific conditions, and researchers have often requested direct access to those databases to get the names of potential subjects for their studies. They then contact those subjects to request their consent to participate in research. However, in getting the names of the potential subjects from the database, the researchers have received confidential information about the

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.

The patient in a persistent vegetative state (hereafter, the PVS patient) has played a central role in recent American bioethical discussions and in recent litigation involving bioethical issues. From Quinlan’ to Cruzan and Wanglie, some of the most important cases involving ethical issues at the end of life have involved PVS patients. Major American medical groups such as the AMA and the American Academy of Neurology have adopted important policy statements on the care of such patients, statements that have been followed by at least one European group.I have always found this activity a bit of a mystery. There is, after all, a relatively clear consensus about decision-making at the end of life, a consensus embodied in such documents as a report from the President's Commission and a report from the Hastings Center.

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.

As various societies have created public commissions to help develop proposals for public policies relating to issues in bioethics, philosophers have sometimes been called upon to serve on the staff of, or to provide consultation to, these public bodies. This issue of the Journal is devoted to examining problems that arise as one tries to articulate the proper role of philosophers serving in these capacities. It includes articles by Frances M. Kamm ("The philosopher as insider and outsider"), Martin Benjamin ("Philosophical integrity and policy development in bioethics"), Richard W. Momeyer ("Philosophers and the public policy process: inside, outside, or nowhere at all?"), Paul T. Menzel ("Public philosophy: distinction without authority"), and E. Haavi Morreim (Physician investment and self-referral: philosophical analysis of a contentious debate").

This paper identifies four major forms of scholarship in bioethics: empirical research, the articulation of mid-level principles of bioethics, the relating of these principles to fundamental moral theories, and discussions of the bioethical implications of legal principles and health delivery policies. It develops a reflective equilibrium approach to the relation between these four forms of scholarship. It then presents, in light of this approach, criteria for quality research in each of these forms of scholarship in bioethics.

Psychiatrists are called upon by the legal system to provide many services. This is particularly true, of course, of forensic psychiatrists. As Bloom and Rogersl have pointed out, psychiatric input often seems mandated by statutes, even though this does not necessarily mean that any particular psychiatrist is required to participate in the proceeding in question. This use of psychiatry has resulted in many criticisms and questions. This chapter will focus on one set of criticisms related to the willingness and capacity of psychiatrists to predict dangerousness.

n the early 199os, the National Institutes of Health (NIH) adopted a policy for the management of conflicts of interest on the part of clinical investigators (45 CFR 50.6045). This policy emphasized disclosure of potential or actual conflicts to institutional officials who would then develop strategies for managing them. The policy was adopted as an alternative to an earlier proposal that had emphasized mandated standards and mandated external disclosures.' Recent studies of the actual operation of conflict of interest policies cast doubt on the adequacy of the approach adopted by the NIH.',3 They indicate that as a result of the discretion allowed to institutional officials, there currently exist few uniform standards and very little accountability. These studies have suggested that to increase accountability, the scope of disclosure should be widened.

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.