Ethical issues in research and innovative therapy in children with mood disorders.

Research involving children with mood disorders should generally offer a reasonable prospect of benefit to those involved, unless the risks are minimal. While federal regulations require a prospect of direct benefit, from an ethical perspective indirect benefits, such as the advantages of being in a clinical trial, are relevant. Standard care should not be presumed to be preferable to treatment in the context of a clinical trial, particularly if it has not been evaluated in well designed studies involving groups comparable to the patient. Similarly, active treatments in a controlled trial should not be presumed to be preferable to placebos, particularly in studies involving mood disorders where the placebo effect is more likely to be substantial. Innovative therapy-using approved drugs for unapproved purposes-may be more problematic than research, on theoretical and empirical grounds. Studies with no prospect of direct benefit and more than minimal risk are problematic when the patient is incompetent to provide meaningful consent. Whether or not a controlled trial involving children with mood disorders can be ethically justified depends on several factors, including the validity of standard treatment, the seriousness of the disorder, the likelihood of adverse consequences if treatment is delayed, the burden of the proposed intervention, and value judgments by parents, working collaboratively with a caring physician.

Counseling families who have a child with a severe congenital anomaly.

The birth of an infant with a major congenital malformation is experienced by the family as a calamity. Parents have an urgent need for compassionate and skilled attention, and a long-term need for counseling to help them adapt to the crisis. The difficult ethical and legal implications of such cases further complicate the doctor's ability to care for the patient and family. Potential conflicts of interest have recently led to the use of voluntary consultation by hospital committees, or obligatory involvement by the courts.

Cystic fibrosis newborn screening: impact on reproductive behavior and implications for genetic counseling.

OBJECTIVE: To evaluate the impact of newborn screening for cystic fibrosis (CF) on the reproductive knowledge and behavior of CF families and to determine if heterozygote detection with the immunoreactive trypsinogen (IRT) method in conjunction with DNA analysis (IRT/DNA) influences knowledge and attitudes about reproduction in false-positive families. METHODS: The Wisconsin CF Neonatal Screening Project investigated 650 340 infants from 1985 to 1994 in a comprehensive randomized controlled trial to study both benefits and risks of newborn screening and to determine if early diagnosis would improve the prognosis of children with CF. Assessments of reproductive knowledge, attitudes, and behaviors of 135 families of children diagnosed as having CF in both the early treatment group and control groups were made 3 months after diagnosis using a questionnaire which was completed by 100 families. The same questionnaire was administered 1 year later to evaluate retention of information. It was completed by 71 families. A follow-up assessment tool was also administered in 1994 and responses obtained from 73 families. Knowledge, attitudes, and behavior among false-positive families were also assessed at the time of the sweat test in 206 families who experienced IRT screening and 109 families tested with the IRT/DNA method. Follow-up assessments were completed 1 year later in 106 IRT families and 63 IRT/DNA families. RESULTS: In families with a CF child, 95% initially understood that there was a 1 in 4 risk in subsequent pregnancies, and there was good retention of this information 1 year later. At the 1994 assessment, 52% of families had not yet conceived more children, but 74% of these already had children. In the couples in whom CF was diagnosed in the first child, 70% (95% confidence interval = 54% to 85%) conceived more children. There were 43 subsequent pregnancies in 31 families. Prenatal diagnosis was used by 26% of the families (8/31) for 21% of the pregnancies (9/43). There were 3 pregnancies with CF detected, all of which were carried to term. In the false-positive groups, >95% of families initially understood that their child definitely did not have CF. There was no difference between false-positive IRT and IRT/DNA groups, and the information was retained at 1 year. Follow-up assessment 1 year after negative sweat tests revealed that 7% of the IRT and 10% of the IRT/DNA families still thought about the results often or constantly. When asked whether the experience of screening affected feelings about having more children, an affirmative response was obtained in 4% of IRT families but in 17% of IRT/DNA families. One year later, more than half of the false-positive IRT/DNA families did not understand that they were at increased risk of having a child with CF. CONCLUSIONS: We conclude that CF neonatal screening does not have a significant impact on the reproductive behavior of most families and that prenatal diagnosis is not used by the majority of CF families. IRT/DNA testing experiences seem to affect attitudes about having more children, and some parents are confused about the implications of the results, even with genetic counseling. However, persistent concerns about the sweat test result are limited. Questions raised by this study confirm the need for more research regarding the process of genetic counseling and its impact on reproductive attitudes and behavior in the newborn screening setting.

Education about genetic testing for breast cancer susceptibility: patient preferences for a computer program or genetic counselor.

The purpose of this study was to describe and compare patient preferences for a genetic counselor or an interactive computer program for various components of genetic education and counseling for breast cancer susceptibility. As part of a randomized intervention study on genetics education and counseling for breast cancer risk, 29 women at moderate risk were educated by both a genetic counselor and an interactive computer program. After both educational interventions, participants completed Likert-style and open-ended questionnaires about what they liked most and least about each intervention, and whether they preferred the counselor or computer for a variety of tasks. Participants were largely satisfied with both the computer program and the genetic counselor. A majority preferred the genetic counselor for addressing their concerns, discussing options and alternatives, being sensitive to emotional concerns, helping to make a decision, being a good listener, assuring understanding, helping to make a good choice, helping to understand genes and breast cancer, telling them what they needed to know, being respectful, setting a relaxed tone, and putting them at ease. However, a majority of the women either preferred the computer program or were neutral about allowing patients to learn at their own pace, helping to avoid embarrassment, making good use of time, explaining genes and breast cancer, and treating the patient as an adult. Qualitative analysis of open-ended questions affirmed that patients valued the personal interactions with the counselors, and liked having their specific questions answered. They liked that the computer was self-paced, informative and private, and could be used without causing embarrassment. We concluded that a computer literate, mostly white group of women at moderate risk for inherited susceptibility to breast cancer preferred interacting with a genetic counselor for personal, individualized components of the genetic counseling process, but accepted or preferred a computer program for being self-paced, private, and informative. By incorporating such a computer program into the genetic education process, it is possible that genetic counselors would be able to spend more time performing the personal, individualized components of genetic counseling.

An interactive computer program can effectively educate patients about genetic testing for breast cancer susceptibility.

As genetic testing for susceptibility to breast cancer becomes more widespread, alternative methods for educating individuals prior to testing will be needed. Our objective was to compare face-to-face education and counseling by a genetic counselor with education by an interactive computer program, assessing the effects of each on knowledge of breast cancer genetics and intent to undergo genetic testing. We used a randomized, controlled trial. Seventy-two self-referred women with a first-degree relative with breast cancer received outpatient education and counseling at the Clinical Center of the National Institutes of Health (NIH). Twenty-nine received individualized counseling from a genetic counselor (counseling group), 29 received education from an interactive computer program followed by individualized counseling (computer group), and 14 were controls. Both pre- and postintervention assessment of knowledge about breast cancer genetics and intent to undergo genetic testing were measured. The control group participants correctly answered 74% of the knowledge questions; the counselor group, 92%; and the computer group, 96% (P <.0001). Unadjusted mean knowledge scores were significantly higher in the computer group than the counselor group (P =.048), but they were equivalent when adjusted for demographic differences (P = 0.34). Intent to undergo genetic testing was influenced by the interventions: preintervention, a majority in all groups (69%) indicated that they were likely (definitely and most likely) to undergo testing; after either intervention coupled with counseling, only 44% indicated that they were likely to do so (P =.0002; odds ratio = 2.8, 95% CI = 1.7-4.9). We concluded that a computer program can successfully educate patients about breast cancer susceptibility, and, along with genetic counseling, can influence patients' intentions to undergo genetic testing.

Ethical dilemmas in child and adolescent consultation psychiatry.

Ethical issues in child and adolescent psychiatry consultation arise frequently but seldom are discussed in a public setting. This case of an adolescent victim of a surgical accident illustrates many aspects of consultation psychiatry. The consult question itself, of behavior management, is not unusual, although in this case the question is complicated by the sequelae of trauma, psychosocial chaos, and the staff's angry feelings toward the patient. In addition, potential surgical wrongdoing at the referring hospital brings up the more difficult ethical questions of the consultant's responsibilities, which must be to the patient and his family, as well as to the attending and referring physicians.

Ethical dilemmas in medical innovation and research: distinguishing experimentation from practice.

The words research and experimentation continue to have the power to evoke fear in potential subjects. But much of standard practice, particularly in critical care settings, involves interventions of unknown efficacy and safety. Innovation also abounds in practice settings, typically unchecked by prospective or retrospective review. Historical attention has focused on the conflict of interest of the physician/investigator, but contemporary safeguards have reduced the risks of research and increased the likelihood that the patient/subject will have the opportunity to make an informed choice. Innovation and untested interventions in practice, in contrast, are often unknown to the patient and lack institutional safeguards. Some common cliches that suggest that research is more to be feared than standard practice will be examined, leading to the following conclusions: defining an intervention as experimental may be less important in ethical terms than the quality of prospective and retrospective review and the standards for informed consent, and the concerns that led to regulation of research should now be directed toward unproven interventions and innovation in the practice setting.

Who should provide genetic education prior to gene testing? Computers and other methods for improving patient understanding.

As numerous new gene tests are introduced into clinical practice, patients have a growing need for accurate and comprehensive information about the risks and benefits of gene testing. However, in the changing healthcare environment, it is not clear who will provide such information because genetic counselors are scarce and their services are not widely utilized, and primary care providers lack time and expertise in genetics. Interactive computers may help fill the information gap. We review a variety of educational modalities for providing patient education and argue that interactive computers have potential advantages over other educational methods for providing information and promoting informed consent to genetic testing. Finally, some questions for further research are raised.

Treatment of seriously ill and handicapped newborns.

Medical technology makes it increasingly possible to prolong life, sometimes indefinitely in the face of overwhelming disability or suffering; thus, choices must be made whether to withhold or withdraw life-sustaining treatment. Reasonable people disagree about who should make such decisions when the patient is an infant, and what principles or rules should guide them. The article briefly reviews the recent history of this controversy analyzes the major ethical substantive principles that have been proposed to guide conduct, and presents the arguments for a procedural approach that is now attracting interest.

Ethical issues in genetics.

Clinical genetics encompasses all ethical issues in medicine and health care. Geneticists, like all health care practitioners, regularly encounter problems of truth telling, paternalism, confidentiality, and rationing. The facts and circumstances under which familial ethical questions arise differ among specialties, but the underlying ethical questions cut across disciplines. The purpose of this article is to provide a review of the ethical issues that commonly arise in the clinical practice of genetics. Accordingly, the goal is primarily to identify common positions and justifications for various approaches as well as to identify consensus where they seem to exist.

Removing organs from anencephalic infants: ethical and legal considerations.

Removing organs from anencephalic infants for transplantation into other infants offers benefits to the recipients, the family of the anencephalic infant, and to society. No interest of the anencephalic infant appears to be violated. Nonetheless, there are serious ethical and legal barriers to such proposals, primarily owing to risks for other patients whose interests might be at risk if barriers against killing were weakened. Five proposals for avoiding these pitfalls are analyzed. There should be consensus on the justifications for such transplants before the practice becomes accepted.

Parents' knowledge of neonatal screening and response to false-positive cystic fibrosis testing.

Neonatal screening for cystic fibrosis (CF) has become feasible through analyzing dried blood specimens for immunoreactive trypsinogen (IRT), but the benefits and risks of such a screening program remain to be delineated. This study, a survey of the parents of 104 Wisconsin infants with false-positive IRT tests, showed parents had knowledge deficits about neonatal screening in general, misconceptions about test results, and high levels of anxiety. Parenting behaviors were reportedly unchanged during the usual 3-day waiting period between the news of the abnormal screening test and the diagnostic sweat test. Most, but not all, parents were relieved by negative sweat test results subsequent to the abnormal IRT test. Factors associated with continued parental concern included having less than a high school education and/or having an infant with low Apgar scores. Additionally, those contacted by telephone were more likely to have misinformation and lingering concerns about the presence of CF in their child.

Ethical considerations surrounding first time procedures: a study and analysis of patient attitudes toward spinal taps by students.

A patient is not always told when a student is performing a procedure for the first time. Withholding this information is a form of deception. It is justified on paternalistic grounds (it is in the patient's interest not to know), or on public policy grounds (given the choice, patients would refuse, thus compromising the training of future physicians). Using the spinal tap procedure (lumbar puncture) as a paradigm, 173 patients were surveyed to determine how they felt about first time procedures by medical students, interns, and residents. The patients indicated that they would be willing to be the subject for a student's (52%), intern's (62%), or resident's (66%) first spinal tap. This paper reassesses the ethics of consent for first time procedures based on responses to this survey.

Parents as decision makers for children.

The continuing high incidence of abuse and neglect requires limits to parental authority over children. Although most parents believe they act in the interests of their children, that alone would not justify interference with a child's liberty. In the area of health care, allowing children some independence from parental control serves three functions: physical protection; respect for autonomy; and protection of public health interests. Despite all that, parents need and deserve to be left alone within broad limits of tolerance, for their sake as well as that of their children.

Current issues in neonatal screening for cystic fibrosis and implications of the CF gene discovery.

Many questions remain regarding the efficacy, toxicity, and costs of CF neonatal screening. It would be premature, in our opinion, to implement mass population screening of newborns for CF until the benefits and risks have been fully defined, and an adequate and logistically feasible testing system developed and/or highly effective therapy for CF lung disease becomes available. In addition, the ethical issues described herein need to be resolved. This pertains not only to the CF patient but also the heterozygote carrier. These reservations notwithstanding, the discovery of the CF gene should have a favorable impact both directly and indirectly on neonatal screening for the disease. Mutation analysis coupled to IRT testing seems most attractive at this time, at least on a research basis, but primary molecular diagnostic procedures might supervene in the future, particularly if they are financially feasible.

Organs from anencephalic infants: an idea whose time has not yet come.

KIE: The application of vigorous life support to anencephalic infants in anticipation of whole brain death and subsequent organ removal leaves unresolved theoretical and empirical questions about the occurrence of brain death in ventilated anencephalic infants and raises concerns about administering intensive care to a living patient for the sole benefit of others. Attempts to resolve these questions by reconsidering the accepted definition of death as requiring death of the whole brain or by advocating the statutory creation of a new category of "brain absent" to identify anencephalic infants or by abandoning the dead donor rule are rejected in favor of a moratorium on transplantation involving anencephalic infants while we gather facts, debate the issues, and develop consensus.^ieng

Putting hospitals on notice.

KIE: Shortly after a well-publicized Indiana case in which a Down's syndrome newborn was allowed to die, the Department of Health and Human Services notified hospitals that, under Section 504 of the Rehabilitation Act of 1973, they could lose federal funding for withholding treatment or nourishment from the handicapped. Fost analyzes ambiguities in Section 504 which might inappropriately justify nontreatment, or require treatment that is neither medically nor morally justified. He suggests alternative approaches to decision making for handicapped newborns. Included with the article are the texts of the DHHS notice and of proposed federal legislation, the "Handicapped Infants Protection Act."^ieng

Banning drugs in sports: a skeptical view.

Recent proposals to punish athletes for taking drugs or to impose mandatory drug testing cannot be defended in ethical terms. Nor is it possible to distinguish consistently between ethical and unethical uses of restorative drugs, additive drugs, painkillers, and recreational drugs. We oppose drugs in sports because they violate the majority notion of acceptable behavior. But such opposition has more to do with defending the ideals of the community than with creating policies that are ethically sound.

The baby in the body.

KIE: The case presented here involves an accident victim who is brain dead, unmarried, and 15 weeks pregnant. The woman's parents ask that she be removed from the ventilator and her body given to them for burial. The putative father of the fetus wants the medical team to attempt to maintain the woman on life-support until the fetus can be delivered with a good chance for survival. The questions presented to the commentators, Norman Fost and Laura Purdy, ask (1) should the physicians try to sustain the pregnancy (for at least 15 weeks)? (2) what are the parents' duties and (3) what obligations are owed to the father?^ieng