Thomas H. Murray

Newborn screening technology: proceed with caution.

The American College of Medical Genetics (ACMG) recommends a significant expansion in the number of conditions targeted by newborn screening (NBS) programs.1 In this commentary we advocate a more cautious approach. NBS dates to the early 1960s, when the technology developed to conduct large-scale testing on dried blood spots for phenylketonuria (PKU).2 PKU remains the paradigm condition for NBS because of features of the disease and its treatment, which are particularly advantageous to population screening. It is a condition that silently causes neurologic devastation but is amenable to early detection and effective prevention with a diet of moderate burden and complexity.3 Many children affected with PKU and their families have benefited from state screening programs over the past 4 decades because of collaboration between health departments, families, primary care providers, and metabolic specialists. However, PKU screening is not an unmitigated success.4,5 There was initial uncertainty about whether children with variant forms of hyperphenylalaninemia required treatment and about whether affected children require life-long dietary management.6 Indeed, some children with benign conditions were seriously harmed from unnecessary restrictions in their diets.5 In addition, long-term studies demonstrate decrements in cognitive function for affected children and adolescents who are not fully adherent to the diet,7,8 yet adherence to the diet is challenging because of its poor palatability, high cost, and limits on insurance coverage in many policies. Affected women who are off the diet are at high risk of bearing severely neurologically impaired children.9 Only recently have many programs begun tracking affected women to enable notification, education, and management. These difficulties by no means negate the value of NBS for PKU, but they highlight the problems with the successful implementation of a population-based screening program even when a model condition is targeted. … Address correspondence to Jeffrey R. Botkin, MD, MPH, Research Administration Building, 75 South 2000 East #108, Salt Lake City, UT 84112-8930. E-mail: jeffrey.botkin{at}hsc.utah.edu

Facilitating participatory decision-making: what happens in real-world community practice?

Background.Participatory decision-making (PDM), a widely held ideal, depends on physician facilitation of patient participation. However, little is known about how PDM facilitation is actualized in outpatient primary care. Objectives.The objective of this study was to describe the prevalence of physician facilitation of PDM in community family practices and associated physician, patient, and visit characteristics. Research Design.This was a cross-sectional observational study. Subjects.The study included 3,453 patients seen by 138 family physicians in 84 community practices. Main Outcome Measures.Research nurses directly observed PDM facilitation in consecutive adult outpatient visits. The association between PDM facilitation and patient, physician, and visit characteristics was assessed with multilevel multivariable regression. Results.PDM facilitation occurred during 25% of observed patient visits. Rates varied considerably among physicians, from 0% to 79% of visits. Patient satisfaction was not associated with PDM facilitation. In multivariable analyses, employed physicians, chronic illness visits, longer visit duration, and visits involving referral were independently associated with PDM facilitation. Visits in which greater time was spent planning treatment and conducting health education were also more likely to involve facilitation of PDM. Conclusions.Community family physicians facilitate PDM at highly variable rates but focus it on patients with the greatest medical needs and most complex levels of decision making. This selective approach appears to meet patient expectations, because PDM facilitation and patient satisfaction are not associated. If patient participation is to be more widely incorporated into outpatient primary care, it must be addressed within the complexity and multiple demands of community practice.

HUGO Urges Genetic Benefit-Sharing

In view of the fact that for-profit enterprise exceeds public expenditures on genetic research and that benefits from the Human Genome Project may accrue only to rich people in rich nations, the HUGO Ethics Committee discussed the necessity of benefit-sharing. Discussions involved case examples ranging from single-gene to multifactorial disorders and included the difficulties of defining community, especially when multifactorial diseases are involved. The Committee discussed arguments for benefit-sharing, including common heritage, the genome as a common resource, and three types of justice: compensatory, procedural, and distributive. The Committee also discussed the importance of community participation in defining benefit, agreed that companies involved in health have special obligations beyond paying taxes, and recommended they devote 1–3% of net profits to healthcare infrastructure or humanitarian efforts.

Are the New Policies on Hyperandrogenism in Elite Female Athletes Really Out of Bounds? Response to “Out of Bounds? A Critique of the New Policies on Hyperandrogenism in Elite Female Athletes”

Women are participating in sport in ever-increasing numbers. Those with the opportunity to compete at the elite level should be provided with a fair chance to win based on their talent and dedication. One of the ways this has been accomplished is that in those sports where men have had a decisive advantage, women and men compete against their own sex. Over time, as women have had more opportunities to develop their talents, the differences in performance between male and female athletes have diminished. But it remains the case that on the elite level, few women would be rated among the 100 best men in most events. The world records for men in sports that rely on strength or size are on the average 10% better than for women. The male advantage in certain sports is most likely explained by the fact that men produce much higher levels of androgenic hormones, most notably testosterone. Men have on average about 10 times higher concentrations of testosterone in the blood thanwomen have. However, some rare conditions in women may cause a greatly increased production of testosterone, leading to serum testosterone levels, and the athletic advantages that come with them, in the range more typically found in males. Concerns for fairness for women athletes led the International Associa-

Who owns the body? On the ethics of using human tissues for commercial purposes.

and look at our current practices for what they can tell us about the moral dimension of our relationship with our physical bodies. First, I will look at three ways of thinking about our tissues, organs, and bodily products. Second, I will try to understand where the current controversy fits within those three models. And third, I will explore the implications of this, and other ethical co cerns, for making public policy on human biologicals. Along the way I will address the issues of informed consent in medicine and research, and of the ownership of human biological products.

IRB practices and policies regarding the secondary research use of biospecimens.

BackgroundAs sharing and secondary research use of biospecimens increases, IRBs and researchers face the challenge of protecting and respecting donors without comprehensive regulations addressing the human subject protection issues posed by biobanking. Variation in IRB biobanking policies about these issues has not been well documented.MethodsThis paper reports on data from a survey of IRB Administrative Directors from 60 institutions affiliated with the Clinical and Translation Science Awards (CTSAs) about their policies and practices regarding secondary use and sharing of biospecimens. Specifically, IRB ADs were asked about consent for future use of biospecimens, assignment of risk for studies using biobanked specimens, and sharing of biospecimens/data.ResultsOur data indicate that IRBs take varying approaches to protocol review, risk assessment, and data sharing, especially when specimens are not anonymized.ConclusionUnclear or divergent policies regarding biospecimen research among IRBs may constitute a barrier to advancing genetic studies and to inter-institutional collaboration, given different institutional requirements for human subjects protections.

Publishing SNP genotypes of human embryonic stem cell lines: policy statement of the International Stem Cell Forum Ethics Working Party.

Novel methods and associated tools permitting individual identification in publicly accessible SNP databases have become a debatable issue. There is growing concern that current technical and ethical safeguards to protect the identities of donors could be insufficient. In the context of human embryonic stem cell research, there are no studies focusing on the probability that an hESC line donor could be identified by analyzing published SNP profiles and associated genotypic and phenotypic information. We present the International Stem Cell Forum (ISCF) Ethics Working Party’s Policy Statement on “Publishing SNP Genotypes of Human Embryonic Stem Cell Lines (hESC)”. The Statement prospectively addresses issues surrounding the publication of genotypic data and associated annotations of hESC lines in open access databases. It proposes a balanced approach between the goals of open science and data sharing with the respect for fundamental bioethical principles (autonomy, privacy, beneficence, justice and research merit and integrity).

Stirring the Simmering “Designer Baby” Pot

How much discretion should parents be granted in determining what sort of child they have? In February 2014, the U.S. Food and Drug Administrations (FDAs) Cellular, Tissue, and Gene Therapies Advisory Committee met to consider the possibility of future clinical trials that would test mitochondrial manipulation technologies for two purposes: to treat infertility and to prevent the transmission of mitochondrial disease from women to their future children. This meeting focused on scientific, technological, and clinical issues. The FDA acknowledged “ethical and social policy issues related to genetic modification of eggs and embryos” but chose not to engage with them, at least not yet (1). Good ethics begins with good facts, but the effort by the FDA to get the facts straight is just the beginning, not the end, of the conversation we must have on the wisdom of mitochondrial manipulation and other reproductive technologies that potentially provide parents with more of a say about the children they have. Preventing a lethal disease is one thing; choosing the traits we desire is quite another.

Divided Loyalties in Sports Medicine

A physicians first duty is to the patient. But this age-old rule takes on new connotations when a third party enters the picture. And when the patient is an athlete, short-term goals often blur long-term risks.

Proposed regulations for research with biospecimens: Responses from stakeholders at CTSA consortium institutions

Secondary research with biospecimens acquired through clinical care and through research is often conducted without the informed consent of individuals from whom the specimens were acquired. While such uses are consistent with the current federal regulations, surveys of the general public suggest that many individuals would prefer more information and choice regarding research use of biospecimens. The federal government issued an Advance Notice of Proposed Rulemaking (ANPRM) in 2011 that proposed a number of potential changes in the regulations governing human subjects. These proposed regulations are particularly pertinent to institutions committed to research involving human subjects—including institutions in the NIH‐funded Clinical and Translational Science Awards (CTSA) consortium. In this study, we reviewed public responses by CTSA‐funded institutions and CTSA‐affiliated organizations and groups regarding the proposed changes in the ANPRM with respect to research with biospecimens. Our results indicate that the majority of responses to the ANPRM from CTSA institutions were not supportive of the proposed changes. While many responses acknowledge a need to change current research practices regarding biospecimens, the proposed changes in the ANPRM received only limited support from this subgroup of academic research institutions.