Toward Improving Practices for Submission of Diagnostic Tissue Blocks for National Cancer Institute Clinical Trials.

OBJECTIVES: The National Cancer Institute (NCI) National Clinical Trials Network performs phase II and III clinical trials, which increasingly rely on the submission of diagnostic formalin-fixed, paraffin-embedded tissue blocks for biomarker assessment. Simultaneously, advances in precision oncology require that clinical centers maintain diagnostic specimens for ancillary, standard-of-care diagnostics. This has caused tissue blocks to become a limited resource for advancing the NCI clinical trial enterprise and the practice of modern molecular pathology. METHODS: The NCI convened a 1-day workshop of multidisciplined experts to discuss barriers and strategic solutions to facilitate diagnostic block submission for clinical trial science, from the perspective of patient advocates, legal experts, pathologists, and clinical oncologists. RESULTS: The expert views and opinions were carefully noted and reported. CONCLUSIONS: Recommendations were proposed to reduce institutional barriers and to assist organizations in developing clear policies regarding diagnostic block submission for clinical trials.

Constitutional Challenges to Liver Transplant Policy.

BACKGROUND: Liver transplant candidacy determination can be contentious. When transplantation is declined for reasons perceived as violating fundamental rights or discriminating against a protected class-for example, age, race, religion, nationality-the case may involve a constitutional claim. Judicial review of such cases may result in decisions with sweeping implications for transplant policy. METHODS: We reviewed all published court opinions involving liver transplantation in 2 legal databases (Lexis Nexus and WestLaw). We included all cases that involved a denial of liver transplant candidacy in violation of constitutional rights. RESULTS: The search returned 1562 cases: 290 involved the denial of insurance coverage for a transplant due to a patient's failure to abstain from drinking, 273 cases involved incarcerated inmates who were denied a liver transplant, 2 involved a constitutional claim for patient requesting a bloodless transplant for religious reasons, and 2 cases arose from age discrimination in transplant criteria. These cases highlight legal pitfalls related to the First Amendment (religious freedom), Eighth Amendment (cruel and unusual punishment), and the Fourteenth Amendment (equal protection and due process). CONCLUSIONS: The risk of a constitutional claim highlights concrete steps needed to ensure the equity of transplant policy. These include efforts to standardize transplant candidacy criteria across payers for candidates with alcohol-related liver disease and advanced age. Efforts to constrain emerging liabilities related to the citizenship of transplant candidates and the definition of donor service areas are also discussed.

Including ELSI research questions in newborn screening pilot studies.

BACKGROUND: The evidence review processes for adding new conditions to state newborn screening (NBS) panels rely on data from pilot studies aimed at assessing the potential benefits and harms of screening. However, the consideration of ethical, legal, and social implications (ELSI) of screening within this research has been limited. This paper outlines important ELSI issues related to newborn screening policy and practices as a resource to help researchers integrate ELSI into NBS pilot studies. APPROACH: Members of the Bioethics and Legal Workgroup for the Newborn Screening Translational Research Network facilitated a series of professional and public discussions aimed at engaging NBS stakeholders to identify important existing and emerging ELSI challenges accompanying NBS. RESULTS: Through these engagement activities, we identified a set of key ELSI questions related to (1) the types of results parents may receive through newborn screening and (2) the initiation and implementation of NBS for a condition within the NBS system. CONCLUSION: Integrating ELSI questions into pilot studies will help NBS programs to better understand the potential impact of screening for a new condition on newborns and families, and make crucial policy decisions aimed at maximized benefits and mitigating the potential negative medical or social implications of screening.

Duchenne Muscular Dystrophy Newborn Screening, a Case Study for Examining Ethical and Legal Issues for Pilots for Emerging Disorders: Considerations and Recommendations.

Duchenne muscular dystrophy (DMD/Duchenne) is one of the ten most severe and common pediatric genetic diseases and affects an estimated 1 in every 5000 male births. While Duchenne is a 100% fatal disease, the clinical community has demonstrated that immediate identification and early clinical interventions can add years, even decades to an individual's life span. In anticipation of the changing therapeutic landscape for the Duchenne community, Parent Project Muscular Dystrophy established a newborn screening (NBS) initiative. This initiative included a Bioethics and Legal Issues Workgroup to consider the bioethics and legal issues of NBS for Duchenne. The workgroup's discussion focused only on Duchenne NBS and met through conference calls over a one-year period of time seeking consensus on various identified issues. This article reports on the findings and recommendations from that workgroup.

Do US Medical Licensing Applications Treat Mental and Physical Illness Equivalently?

BACKGROUND AND OBJECTIVES: State medical licensing boards are responsible for evaluating physician impairment. Given the stigma generated by mental health issues among physicians and in the medical training culture, we were interested in whether states asked about mental and physical health conditions differently and whether questions focused on current impairment. METHODS: Two authors reviewed physician medical licensing applications for US physicians seeking first-time licensing in 2013 in the 50 states and the District of Columbia. Questions about physical and mental health, as well as substance abuse, were identified and coded as to whether or not they asked about diagnosis and/or treatment or limited the questions to conditions causing physician impairment. RESULTS: Forty-three (84%) states asked questions about mental health conditions, 43 (84%) about physical health conditions, and 47 (92%) about substance use. States were more likely to ask for history of treatment and prior hospitalization for mental health and substance use, compared with physical health disorders. Among states asking about mental health, just 23 (53%) limited all questions to disorders causing functional impairment and just 6 (14%) limited to current problems. CONCLUSIONS: While most state medical licensing boards ask about mental health conditions or treatment, only half limited queries to disorders causing impairment. Differences in how state licensing boards assess mental health raise important ethical and legal questions about assessing physician ability to practice and may discourage treatment for physicians who might otherwise benefit from appropriate care.

"I would never want to have a mental health diagnosis on my record": A survey of female physicians on mental health diagnosis, treatment, and reporting.

INTRODUCTION: Physicians have high rates of suicide and depression. Most state medical boards require disclosure of mental health problems on physician licensing applications, which has been theorized to increase stigma about mental health and prevent help-seeking among physicians. METHODS: We surveyed a convenience sample of female physician-parents on a closed Facebook group. The anonymous 24-question survey asked about mental health history and treatment, perceptions of stigma, opinions about state licensing questions on mental health, and personal experiences with reporting. RESULTS: 2106 women responded, representing all 50 states and the District of Columbia. Most respondents were aged 30-59. Almost 50% of women believed that they had met the criteria for mental illness but had not sought treatment. Key reasons for avoiding care included a belief they could manage independently, limited time, fear of reporting to a medical licensing board, and the belief that diagnosis was embarrassing or shameful. Only 6% of physicians with formal diagnosis or treatment of mental illness had disclosed to their state. CONCLUSIONS: Women physicians report substantial and persistent fear regarding stigma which inhibits both treatment and disclosure. Licensing questions, particularly those asking about a diagnosis or treatment rather than functional impairment may contribute to treatment reluctance.

Parental permission for pilot newborn screening research: guidelines from the NBSTRN.

There is broad recognition of the need for population-based research to assess the safety and efficacy of newborn screening (NBS) for conditions that are not on current panels. However, prospective population-based research poses significant ethical, regulatory, and logistical challenges. In the context of NBS, there have been a variety of approaches that address parental decision-making in pilot studies of new screening tests or conditions. This article presents an ethical and legal analysis of the role of parental permission by the Bioethics and Legal Work Group of the Newborn Screening Translational Research Network created under a contract from the National Institute of Child Health and Human Development to the American College of Medical Genetics and Genomics. Circumstances are outlined in which a waiver of documentation of permission or a waiver of permission may be ethically and legally appropriate in the NBS context. These guidelines do not constitute American Academy of Pediatrics policy.

The perils of SNP microarray testing: uncovering unexpected consanguinity.

BACKGROUND: Although single nucleotide polymorphism chromosomal microarrays identify areas of small genetic deletions or duplications, they can also reveal regions of homozygosity indicative of consanguinity. As more nongeneticists order single nucleotide polymorphism microarrays, they must prepare for the potential ethical, legal, and social issues that result from revelation of unanticipated consanguinity. PATIENT: We describe an infant with multiple congenital anomalies who underwent single nucleotide polymorphism microarray testing. RESULTS: The results of the single nucleotide polymorphism microarray revealed several large regions of homozygosity that indicated identity by descent most consistent with a second-degree or third-degree relative mating (e.g., uncle/niece, half-brother/sister, first cousins). The mother was not aware of the test's potential to reveal consanguinity. When informed of the test results, she reluctantly admitted to being raped by her half-brother around the time of conception. CONCLUSIONS: During the pretesting consent process, providers should inform parents that single nucleotide polymorphism microarray testing could reveal consanguinity. Providers must also understand the psychological implications, as well as the legal and moral obligations, that accompany single nucleotide polymorphism microarray results that indicate consanguinity.

Observational study of telephone consults by stroke experts supporting community tissue plasminogen activator delivery.

OBJECTIVES: Barriers to intravenous (IV) tissue plasminogen activator (tPA) use in ischemic stroke include limited treatment experience of community physicians. Models of acute stroke care have been designed to address these limitations by providing community support. These include support by telephone or televideo, with or without subsequent transport to tertiary care centers. The authors describe the frequency, characteristics, and effect of community phone consultations to a 24/7 stroke "hotline" staffed by stroke physicians at an academic stroke center using such a model. METHODS: Twelve intervention hospitals participating in the INcreasing Stroke Treatment through Interventional behavior Change Tactics (INSTINCT) trial were provided a single-access number ("hotline") for expert consultation on tPA use. Experts consisted of stroke-trained physicians at an academic medical center. Hotline use was not mandated by the study protocol, nor was patient transfer required. Consultants were required to record all treatment questions in a Web-based log. All patients discussed over the hotline and/or treated with tPA in an INSTINCT hospital underwent multilevel chart review by trained nurse coordinators. Cases were linked to logged hotline calls, based on the time of treatment and the initial treating hospital. Physician adjudicators assessed appropriateness of tPA treatment, presence of deviation from standard guidelines, and treatment complications (intracranial hemorrhage [ICH], systemic hemorrhage, or death). RESULTS: Over 27 months, there were a total of 204 hotline calls regarding 116 patients. Ninety-one percent of calls were between 8 a.m. and midnight, and 77% of questions explored issues of eligibility for IV tPA, particularly for minor stroke or improving stroke (26%). A total of 243 patients were treated with IV tPA at the 12 intervention hospitals, 54 of which were following hotline consult. Seventy-six percent of hotline patients in whom tPA was recommended actually received tPA, while 2% of those in whom tPA was not recommended received the medication. There were no differences in protocol deviations (27.8% hotline group vs. 23.8% nonhotline group), incidence of symptomatic ICH (5.6% vs. 7.3%), or in-hospital mortality (5.6% vs. 13.2%). No medico-legal issues have been reported for any case in the study. CONCLUSIONS: Providing tPA decision-making support via telephone consult to community physicians is feasible and safe. Consultants may play a more prominent role in determining tPA ineligibility than acceptance. Future work should include a real-time survey of physician providers to ascertain such potential qualitative benefits of a stroke hotline.

Medical, ethical, and legal considerations in fertility preservation.

The past 2 decades have seen a significant rise in cancer survival rates, and an increasing proportion of survivors at reproductive age are interested in childbearing. Although assisted reproduction provides physicians with an array of potential possibilities to help patients whose fertility is compromised by cancer treatment, there is still a dearth of regulation regarding the application of this technology. The present paper reviews the current options for fertility preservation, with a particular focus on the legal and ethical challenges that confront providers of this type of care.

Committee report: Considerations and recommendations for national guidance regarding the retention and use of residual dried blood spot specimens after newborn screening.

Newborn screening programs are state based with variable policies. Guidance regarding the retention, storage, and use of portions of newborn screening dried blood spots that remain after screening (residual specimens) was first published in 1996. Since then, newborn screening programs have paid increased attention to specimen storage and usage issues. Standard residual specimen uses include quality assurance and program evaluation, treatment efficacy, test refinement, and result verification. In all cases, privacy and security are primary concerns. In general, two distinct state practices regarding the storage and use of residual newborn screening specimens exist: (1) short-term storage (<3 years), primarily for standard program uses and (2) long-term storage (>18 years), for standard program uses and possible important public health research uses. Recently, there have been concerns in some consumer communities regarding both the potential uses of residual specimens and patient (newborn and family) privacy. To assist in policy improvements that can protect the individual's privacy and allow for important public health uses of residual newborn screening specimens, the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children has developed recommendations (with requested action by the Secretary where applicable). This report presents the Committee's recommendations and reviews the pertinent associated issues.

Ethical issues in the conduct of clinical trials in obstructive sleep apnea.

Scientifically rigorous clinical trials are needed to test continuous positive airway pressure's (CPAP) effect on important clinical endpoints known to be associated with obstructive sleep apnea, such as myocardial infarction, cardiac arrhythmias, stroke, mortality, seizures, and cognitive function. In this "Special Article," we review the regulatory and ethical issues that surround the design and conduct of CPAP trials, including selection of the appropriate control condition, exclusion criteria, and follow-up duration.

Is the United States ready to embrace concierge medicine?

Concierge medicine (also called retainer practices or consumer-focused care) represents a new approach to the delivery of primary care. This model involves more personalized attention and greater resources for individual patients, thus limiting the number of patients who can be served at each practice. All enrolled members must pay an annual membership fee or retainer. Given the short history and novelty of concierge medicine, this article explores the clinical, economic, marketing, ethical, and policy implications of this innovative approach to primary care.