Protecting the privacy of family members in survey and pedigree research.

The recent controversy at Virginia Commonwealth University involving research ethics raises important and complex issues in survey and pedigree research. The primary questions are whether family members of survey respondents themselves become subjects of the project and if they are subjects whether informed consent must be obtained for investigators to retain private information on these individuals. This article provides an analysis of the ethical issues and regulatory standards involved in this debate for consideration by investigators and institutional review boards. The analysis suggests that strong protections for the rights and welfare of subjects and their family members can be incorporated into survey and pedigree research protocols without hindering projects with extensive consent requirements.

Genetic testing, adverse selection, and the demand for life insurance.

The dramatic increase in genetic testing for adult-onset diseases has created a debate regarding whether or not insurance companies should be able to use genetic test results in underwriting. We use data from women who have been tested for the BRCA1 gene mutation along with data from otherwise comparable untested women to assess the potential for adverse selection in the life insurance market when tested individuals know their genetic test results but insurers do not. Our analyses show that women who test positive for the BRCA1 gene mutation do not capitalize on their informational advantage by purchasing more life insurance than those women who have not undergone genetic testing.

Attitudes toward the genetic testing of children among adults in a Utah-based kindred tested for a BRCA1 mutation.

Advances in molecular biology and genetics have led to the identification of the breast/ovarian cancer susceptibility genes BRCA1 and BRCA2, along with tests to detect mutations in these genes. Although the appropriateness of BRCA1/2 genetic testing for children has been debated in the literature, little is known about the attitudes of individuals who have undergone cancer susceptibility testing. The present study focused on attitudes toward BRCA1 testing for children among 218 adults from a Utah-based kindred who had received BRCA1 test results. Results indicated that approximately one-fourth of the participants would permit BRCA1 testing for children under the age of 18. General attitudes about genetic testing were predictive of attitudes toward the testing of children. In addition, men and individuals without a BRCA1 mutation were more likely to agree that minors should be allowed BRCA1 testing. Individuals whose mother had been affected with breast cancer were less likely to permit testing for minors. Among parents of minor children, less than one-fifth indicated that they would want BRCA1 testing for their own children; carrier status was not predictive of attitudes toward testing their own children. As breast/ovarian cancer susceptibility testing continues to be disseminated into clinical settings, there may be an increase in the number of test requests for minors. The findings of the present study represent an important step in exploring attitudes about genetic testing of children among individuals who have received cancer susceptibility test results.

Can pediatricians define and apply the concept of brain death?

OBJECTIVE: We sought to determine pediatric residents' and attending physicians' ability to define brain death, their ability to apply this standard of death to a clinical scenario, and their knowledge regarding the legal necessity of confirmatory testing when determining death by brain criteria. We compared resident and attending self-confidence at discussing brain death with their ability to define brain death and apply this concept to a clinical scenario. METHODOLOGY: A questionnaire was sent to 136 residents, postgraduate years 1 through 3, at four accredited pediatric training programs in the United States. Participation was tracked by return address. One follow-up request for participation was made. A similar procedure was followed for 140 faculty pediatricians at two of the institutions. Demographic information including level of training, subspecialty training, training program, and formal ethics training was collected. Respondents defined brain death, interpreted a clinical scenario, and stated whether confirmatory testing is legally required to determine death by brain criteria. Respondents rated their confidence at explaining brain death to a patient's family on a scale from 1 to 5. RESULTS: Eighty-seven percent (118/136) of resident surveys were returned. Thirty-six percent (42/118) of the residents correctly defined brain death. Forty-three percent (51/118) of residents correctly interpreted the clinical scenario. Fifty-five percent (65/118) of the residents correctly recognized that brain death could be determined without a confirmatory test. Residents who correctly defined brain death were as confident as those who did not (2.8 +/- 1 vs 1.5 +/- 1). Residents who correctly interpreted the clinical scenario were as confident as those who did not (2.6 +/- 1 vs 1.9 +/- 0.9). Eighty percent (112/140) of attending physician surveys were returned. Thirty-nine percent (44/112) of attending physicians correctly defined brain death. Fifty-three percent (59/112) correctly interpreted the clinical scenario. Fifty-eight percent (65/112) recognized that brain death can be diagnosed without confirmatory testing. All pediatric intensivists (n = 12) correctly answered all three questions. Their performance was significantly better than other pediatricians. Attendings who correctly defined brain death were more confident than those who did not (4.2 +/- 1 vs 1.1 +/- 0. 9). Attendings who correctly interpreted the clinical scenario were more confident than those who did not (3.8 +/- 1.2 vs 2.2 +/- 1.2). CONCLUSIONS: Pediatric residents and attendings have difficulty defining and applying the concept of brain death. This concept is difficult to grasp and internalize for many pediatricians. To ensure that critical decisions are made by knowledgeable physicians and well-informed families, more effective educational strategies need to be identified.

Familial context of genetic testing for cancer susceptibility: moderating effect of siblings' test results on psychological distress one to two weeks after BRCA1 mutation testing.

OBJECTIVES: To determine whether psychological distress differs among individuals tested for a BRCA1 mutation and is moderated by the pattern of their siblings' test results. MATERIALS AND METHODS: Participants in this study are members of a large kindred identified with a BRCA1 mutation. Subjects included 87 males and 125 females who completed a baseline interview, were tested for a BRCA1 gene mutation, received their results in person from a genetic counselor, completed a follow-up interview 1-2 weeks after the receipt of their test results, and had complete data on all variables used in the analysis. The main outcome of the study was psychological distress as measured by the Impact of Event Scale during the 1-2 week follow-up interview. Data were analyzed based on multiple regression. RESULTS: Male carriers, relative to noncarriers, experienced significantly more distress if they were the first tested than when all of their tested siblings were already known to be negative. Noncarrier males whose siblings all tested positive also encountered significant test-related distress. The largest adverse psychological consequences for female carriers, relative to noncarriers, were for those who were tested first and those whose tested siblings were noncarriers. CONCLUSIONS: The familial context in which genetic testing is conducted may be important for understanding how individuals react to their own test results.

Privacy and confidentiality in the publication of pedigrees: a survey of investigators and biomedical journals.

CONTEXT: Pedigree diagrams efficiently communicate family information to genetics investigators; however, the publication of pedigrees poses a risk to the privacy and confidentiality of individuals depicted in the diagrams. Two sets of authoritative guidelines have been published to protect the privacy and confidentiality of subjects, but the influence of these guidelines on publication practices for pedigrees is unknown. OBJECTIVE: To determine the attitudes, practices, and experiences of investigators and journals with respect to privacy and confidentiality concerns in the publication of pedigrees. DESIGN: Investigators who have published pedigrees and editors of 26 biomedical journals were surveyed. Journals were reviewed for content in their "information for authors" sections and for documentation of informed consent in articles containing pedigrees. OUTCOME MEASURES: Practices regarding confidentiality and privacy reported by investigators and editors. RESULTS: Of 226 surveys sent to investigators, 177 were returned (78% response rate). Sixty-one investigators (36%) stated that family members were not informed that their pedigree would be published; 131 (78%) do not obtain informed consent specifically for pedigree publication and only 12 (28%) of the 43 who obtained consent obtained consent from all family members depicted. Thirty-two individuals (19%) reported having altered published pedigrees and 14 (45%) of 31 who had altered pedigrees stated that alterations were not disclosed to journals. Of the 14 journals that responded (54% response rate), only 3 reported written policies for managing potentially identifying information. Two journals reported having asked authors to alter pedigrees and 3 stated they had permitted alterations. A review of 5 genetics journals over a 2-year period revealed no documentation of consent for pedigree publication. CONCLUSIONS: Current practices in the publication of pedigrees do not conform with established recommendations and risk the privacy and confidentiality of subjects, often without informed consent. Attempts to address this problem through the alteration of data are being used, although this practice impairs the integrity of scientific communication.

Ethical issues and practical problems in preimplantation genetic diagnosis.

Author argues the preimplantation genetic diagnosis is ethically acceptable for currently intended uses, but a variety of ethical and practical issues will arise with further development of this technology.

Genetic testing for susceptibility to adult-onset cancer. The process and content of informed consent.

OBJECTIVE: To provide guidance on informed consent to clinicians offering cancer susceptibility testing. PARTICIPANTS: The Task Force on Informed Consent is part of the Cancer Genetics Studies Consortium (CGSC), whose members were recipients of National Institutes of Health grants to assess the implications of cancer susceptibility testing. The 10 task force members represent a range of relevant backgrounds, including various medical specialties, social science, genetic counseling, and consumer advocacy. EVIDENCE: The CGSC held 3 public meetings from 1994 to 1996. At its first meeting, the task force jointly established a list of topics. The cochairs (G.G. and J.R.B) then developed an outline and assigned each topic to an appropriate writer and reviewer. Writers summarized the literature on their topics and drafted recommendations, which were then revised by the reviewers. The cochairs compiled and edited the entire manuscript. All members were involved in writing this report. CONSENSUS PROCESS: The first draft was distributed to task force members, after which a meeting was held to discuss its content and organization. Consensus was reached by voting. A subsequent draft was presented to the entire CGSC at its third meeting, and comments were incorporated. CONCLUSIONS: The task force recommends that informed consent for cancer susceptibility testing be an ongoing process of education and counseling in which (1) providers elicit participant, family, and community values and disclose their own, (2) decision making is shared, (3) the style of information disclosure is individualized, and (4) specific content areas are discussed.

Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium.

OBJECTIVE: To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations associated with hereditary nonpolyposis colon cancer (HNPCC). PARTICIPANTS: A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by the National Human Genome Research Institute (previously the National Center for Human Genome Research). EVIDENCE: Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to colon cancer were identified using MEDLINE and bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "colon cancer," and "screening" in combination with "cancer family" and "HNPCC." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. CONSENSUS PROCESS: The task force developed recommendations through discussions over a 14-month period. CONCLUSIONS: Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on observational studies, colonoscopy every 1 to 3 years starting at age 25 years is recommended for individuals known to have HNPCC-associated mutations. Endometrial cancer screening is also recommended, based on expert opinion concerning presumptive benefit. No recommendation is made for or against prophylactic surgery (ie, colectomy, hysterectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.

Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium.

OBJECTIVE: To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations in the BRCA1 or BRCA2 genes. PARTICIPANTS: A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by National Human Genome Research Institute (previously the National Center for Human Genome Research). EVIDENCE: Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to breast and ovarian cancer were identified using MEDLINE (National Library of Medicine) and from bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "breast cancer," "ovarian cancer," and "screening," or "surveillance" in combination with "cancer family" and "BRCA1" and "BRCA2." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. CONSENSUS PROCESS: The task force developed recommendations through discussions over a 14-month period. CONCLUSIONS: Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on expert opinion concerning presumptive benefit, early breast cancer and ovarian cancer screening are recommended for individuals with BRCA1 mutations and early breast cancer screening for those with BRCA2 mutations. No recommendation is made for or against prophylactic surgery (eg, mastectomy, oophorectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking, and case reports have documented the occurrence of cancer following prophylactic surgery. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.

Psychological responses to BRCA1 mutation testing: preliminary findings.

The short-term psychological responses of 60 adult women tested for a BRCA1 gene mutation associated with a high risk of breast and ovarian cancer were investigated. Participants were members of a large kindred enrolled in an ongoing prospective study of the psychosocial impact of genetic testing. Initial results from participants who completed both the pretest baseline and the 1-2 week posttest follow-up interviews are reported. Gene mutation carriers manifested significantly higher levels of test-related psychological distress, as measured by the Impact of Event Scale, when compared with noncarriers. The highest levels of test-related distress were observed among mutation carriers with no history of cancer or cancer-related surgery. Although general distress (state anxiety) declined after testing, carriers were more distressed than noncarriers at follow-up.

BRCA1 Testing: Genetic Counseling Protocol Development and Counseling Issues.

This article discusses the genetic counseling protocols which were developed and counseling issues that have arisen in the first 2 years of evaluating a large kindred with a BRCA1 mutation. The rationale for the development of the genetic counseling protocols and specific genetic counseling visual aids are presented and discussed. The protocols and counseling aids can serve as models for other programs offering cancer susceptibility testing. The observations of study counselors about study subject concerns and responses to genetic testing at the time of the pretest and posttest counseling sessions are presented.

Advance directives in Utah. Information from death certificates and informants.

BACKGROUND: Advance directives have been studied in different patient populations and institutions. Most reports have shown limited use and little medically observable effect. To our knowledge, no previous study has focused on the use of advance directives by individuals who have died or how their family members perceived the documents' effect. METHODS: We contacted informants listed on Utah Death Certificates from 1992 to estimate the prevalence and effect of advance directives. Eighty-two percent of 1398 informants we contacted agreed to our telephone interview. RESULTS: More than 50% of decedents reportedly completed an advance directive. Individuals older than 65 years (57.3%), women (58.1%), nursing home residents (63.4%), and hospice users (75.2%) were most likely to have had advance directives. Education, religion, religiosity, and location had no effect on prevalence. Most informants stated that advance directives had no effect on the decedent's care, but a minority felt they helped to limit treatment. Do-not-resuscitate orders were written more often for patients with advance directives. Feeding tubes were removed more often from decedents with living wills than from other decedents. Mechanical ventilatory support was not less frequent in patients with advance directives. CONCLUSIONS: Our study confirms others that found little evidence that advance directives affect life-sustaining treatments. In the infrequent situations when they apply, they may be more persuasive than family members in convincing physicians to limit treatment. We observed that survivors had 2 perceptions about advance directives, not emphasized in previous reports, that they seemed to limit treatment and to ease their burden of decision making.

Fetal privacy and confidentiality.

PIP: With the advent of new and better contraceptive methods and the ability to facilitate and manipulate fertilization and gestation, couples will gain greater control over their fertility. Once a pregnancy has been established or an in vitro embryo created, the ability to evaluate the embryo and fetus will increase dramatically with progress in human genetic research. Preconception and preimplantation genetic testing and screening are now possible, and the technology to perform prenatal screening early in gestation is advancing rapidly. Nonsurgical methods facilitate induced abortion with a relatively lower degree of trauma upon the woman undergoing the procedure. These capabilities may all be used to enable and even encourage the genetic selection of future children. Despite the ethical concerns associated with prenatal testing and abortion, these services will continue to be an integral aspect of reproductive medicine. As technology advances, however, it will be possible to test and screen for conditions which do not produce serious defects. Genetic conditions which produce relatively mild impacts upon health will be identifiable in the embryo or fetus, while late-onset conditions and genetic factors which have only a probability of affecting health will also be located in the fetal genome. Prospective parents may therefore soon have the capability of selecting their most desirable embryo in vitro, or terminating all undesirable fetuses in vivo until the preferred child is delivered. The medical profession must take some responsibility for establishing guidelines on the use of reproductive technology. The standards of practice for the medical profession must reflect the results of a broad social debate over competing moral values. The author develops an argument for legal and ethical limitations on the application of prenatal testing and screening technology, suggesting that for some medical conditions, respect for the privacy and confidentiality of the fetus outweighs parental rights to information about the fetus. Preliminary definitions for what constitute serious defects and minor conditions are developed.^ieng

Medical students in a time of HIV: education and the duty to treat.

This article concerns medical education about the ethics of professional duties and treatment of HIV-infected patients. The issue at hand is not whether medical students have a duty to treat HIV-infected patients, since it is a matter of consensus that they do. Medical schools have reasserted that risks are inherent in medicine, and that medical school admission should be based on the willingness to accept some risks, in addition to intelligence and personal skills. Those who wish to avoid risks are free to enter other professions. While it is imperative to assert a duty to treat, this requires thoughtful explanation to match the understandably high anxiety levels of many medical students.