iPS cells: mapping the policy issues.

Given the explosion of research on induced pluripotent stem (iPS) cells, it is timely to consider the various ethical, legal, and social issues engaged by this fast-moving field. Here, we review issues associated with the procurement, basic research, and clinical translation of iPS cells.

From patients to partners: participant-centric initiatives in biomedical research.

Advances in computing technology and bioinformatics mean that medical research is increasingly characterized by large international consortia of researchers that are reliant on large data sets and biobanks. These trends raise a number of challenges for obtaining consent, protecting participant privacy concerns and maintaining public trust. Participant-centred initiatives (PCIs) use social media technologies to address these immediate concerns, but they also provide the basis for long-term interactive partnerships. Here, we give an overview of this rapidly moving field by providing an analysis of the different PCI approaches, as well as the benefits and challenges of implementing PCIs.

Disclosing pathogenic genetic variants to research participants: quantifying an emerging ethical responsibility.

There is an emerging consensus that when investigators obtain genomic data from research participants, they may incur an ethical responsibility to inform at-risk individuals about clinically significant variants discovered during the course of their research. With whole-exome sequencing becoming commonplace and the falling costs of full-genome sequencing, there will be an increasingly large number of variants identified in research participants that may be of sufficient clinical relevance to share. An explicit approach to triaging and communicating these results has yet to be developed, and even the magnitude of the task is uncertain. To develop an estimate of the number of variants that might qualify for disclosure, we apply recently published recommendations for the return of results to a defined and representative set of variants and then extrapolate these estimates to genome scale. We find that the total number of variants meeting the threshold for recommended disclosure ranges from 3955-12,579 (3.79%-12.06%, 95% CI) in the most conservative estimate to 6998-17,189 (6.69%-16.48%, 95% CI) in an estimate including variants with variable disease expressivity. Additionally, if the growth rate from the previous 4 yr continues, we estimate that the total number of disease-associated variants will grow 37% over the next 4 yr.

Innovation incentives or corrupt conflicts of interest? Moving beyond Jekyll and Hyde in regulating biomedical academic-industry relationships.

The most contentious, unresolved issue in biomedicine in the last twenty-five years has been how to best address compensated partnerships between academic researchers and the pharmaceutical industry. Law and policy deliberately promote these partnerships through intellectual property law, research funding programs, and drug and device approval pathways while simultaneously condemning them through conflict-of-interest (COI) regulations. These regulations have not been subjected to the close scrutiny that is typically utilized in administrative law to evaluate and improve regulatory systems. This Article suggests that the solution to this standoff in biomedical law and policy lies in an informed, empirical approach. Such an approach must both recognize such partnerships' legal and practical variations, as well as classify them based on their benefit to innovation and their harm to research biases. Ultimately, this approach must facilitate administrative reforms that would convert what is now an inherently arbitrary, yet widespread, regulatory regime into an epistemically rich mechanism for distinguishing between harmful and beneficial partnerships.

The beliefs, motivations, and expectations of parents who have enrolled their children in a genetic biorepository.

PURPOSE: Little is known about parental attitudes toward return of individual research results (IRRs) in pediatric genomic research. The aim of this study was to understand the views of the parents who enrolled their children in a genomic repository in which IRRs will be returned. METHODS: We conducted focus groups with parents of children with developmental disorders enrolled in the Gene Partnership (GP), a genomic research repository that offers to return IRRs, to learn about their understanding of the GP, motivations for enrolling their children, and expectations regarding the return of IRRs. RESULTS: Parents hoped to receive IRRs that would help them better understand their children's condition(s). They understood that this outcome was unlikely, but hoped that their children's participation in the GP would contribute to scientific knowledge. Most parents wanted to receive all IRRs about their child, even for diseases that were severe and untreatable, citing reasons of personal utility. Parents preferred electronic delivery of the results and wanted to designate their preferences regarding what information they would receive. CONCLUSIONS: It is important for researchers to understand participant expectations in enrolling in a research repository that offers to disclose children's IRRs in order to effectively communicate the implications to parents during the consenting process.

Scientific self-regulation-so good, how can it fail? Commentary on "The problems with forbidding science".

To be a functional alternative to government regulation, self-regulation of science must be credible to both scientists and the public, accountable, ethical, and effective. According to some, serious problems continue in research ethics in the United States despite a rich history of proposed self-regulatory standards and oversight devices. Successful efforts at self-regulation in stem cell research contrast with unsuccessful efforts in research ethics, particularly conflicts of interest. Part of the cause for a lack of success in self-regulation is fragmented, disconnected oversight, and failure to embody genuine scientific and public consensus. To be accountable, credible and effective, self-regulation must be inclusive and multidisciplinary, publicly engaged, sufficiently disinterested, operationally integrated with institutional goals, and must implement a genuine consensus among scientists and the public. The mechanisms of self-regulation must be sufficiently broad in their oversight, and interconnected with other institutional forces and actors, that they do not create fragmented solutions.

Whose personal control? Creating private, personally controlled health records for pediatric and adolescent patients.

Personally controlled health records (PCHRs) enable patients to store, manage, and share their own health data, and promise unprecedented consumer access to medical information. To deploy a PCHR in the pediatric population requires crafting of access and security policies, tailored to a record that is not only under patient control, but one that may also be accessed by parents, guardians, and third-party entities. Such hybrid control of health information requires careful consideration of both the PCHR vendor's access policies, as well as institutional policies regulating data feeds to the PCHR, to ensure that the privacy and confidentiality of each user is preserved. Such policies must ensure compliance with legal mandates to prevent unintended disclosures and must preserve the complex interactions of the patient-provider relationship. Informed by our own operational involvement in the implementation of the Indivo PCHR, we provide a framework for understanding and addressing the challenges posed by child, adolescent, and family access to PCHRs.

Beyond financial conflicts of interest: Institutional oversight of faculty consulting agreements at schools of medicine and public health.

IMPORTANCE: Approximately one-third of U.S. life sciences faculty engage in industry consulting. Despite reports that consulting contracts often impinge on faculty and university interests, institutional approaches to regulating consulting agreements are largely unknown. OBJECTIVE: To investigate the nature of institutional oversight of faculty consulting contracts at U.S. schools of medicine and public health. DESIGN: Structured telephone interviews with institutional administrators. Questions included the nature of oversight for faculty consulting agreements, if any, and views about consulting as a private versus institutional matter. Interviews were analyzed using a structured coding scheme. SETTING: All accredited schools of medicine and public health in the U.S. PARTICIPANTS: Administrators responsible for faculty affairs were identified via internet searches and telephone and email follow-up. The 118 administrators interviewed represented 73% of U.S. schools of medicine and public health, and 75% of those invited to participate. INTERVENTION: Structured, 15-30 minute telephone interviews. MAIN OUTCOMES AND MEASURES: Prevalence and type of institutional oversight; responses to concerning provisions in consulting agreements; perceptions of institutional oversight. RESULTS: One third of institutions (36%) required faculty to submit at least some agreements for institutional review and 36% reviewed contracts upon request, while 35% refused to review contracts. Among institutions with review, there was wide variation the issues covered. The most common topic was intellectual property rights (64%), while only 23% looked at publication rights and 19% for inappropriately broad confidentiality provisions. Six in ten administrators reported they had no power to prevent faculty from signing consulting agreements. Although most respondents identified institutional risks from consulting relationships, many maintained that consulting agreements are "private." CONCLUSIONS AND RELEVANCE: Oversight of faculty consulting agreements at U.S. schools of medicine and public health is inconsistent across institutions and usually not robust. The interests at stake suggest the need for stronger oversight.

Availability and quality of mobile health app privacy policies.

Mobile health (mHealth) customers shopping for applications (apps) should be aware of app privacy practices so they can make informed decisions about purchase and use. We sought to assess the availability, scope, and transparency of mHealth app privacy policies on iOS and Android. Over 35,000 mHealth apps are available for iOS and Android. Of the 600 most commonly used apps, only 183 (30.5%) had privacy policies. Average policy length was 1755 (SD 1301) words with a reading grade level of 16 (SD 2.9). Two thirds (66.1%) of privacy policies did not specifically address the app itself. Our findings show that currently mHealth developers often fail to provide app privacy policies. The privacy policies that are available do not make information privacy practices transparent to users, require college-level literacy, and are often not focused on the app itself. Further research is warranted to address why privacy policies are often absent, opaque, or irrelevant, and to find a remedy.

Position statement on the provision and procurement of human eggs for stem cell research.

The nature of compensation for women who donate eggs (oocytes) for research remains a contentious issue internationally. This position paper lays out the arguments for, and discusses the arrangements in which, a modest payment might be ethically justifiable.

Responsibility rewarded: ethics, engagement, and scientific autonomy in the labyrinth of the minotaur.

Dramatic changes in the stem cell ethical and research ecosystem in the last 10 years depended on active engagement among scientists, ethicists, government, and public. Tracing that story demonstrates the value of such engagement, and forecasts a successful method for meeting future challenges.

Overseeing innovative therapy without mistaking it for research: a function-based model based on old truths, new capacities, and lessons from stem cells.

Should innovative therapy occur only within a research paradigm and under institutional review board oversight? The health risks from current human embryonic stem cell clinical applications have raised again a fundamental question addressed first in papers submitted to inform the writing of the Belmont Report. Revisiting the thinking underlying the Belmont Report, together with examining changed circumstances since then, leads to a new model for overseeing innovative therapy based on its unique risks and context, important changes since the Belmont Report, and new opportunities for addressing risks through safety and quality systems in health care.

State payer mandates to cover care in US oncology trials: do science and ethics matter?

BACKGROUND: In the United States, Medicare-eligible participants' costs for routine care and complications from cancer clinical trials are covered by Medicare, but other people depend on state insurance mandates to assure coverage. METHODS: State mandates were reviewed for requirements to assure trials' scientific and ethical soundness, whom they covered and omitted, scope, and coverage for participants' research-related injuries in addition to routine care costs. RESULTS: Twenty-six states mandated coverage. Four states (15%) required scientific peer review for all studies. For 20 states (80%), an approved investigational new drug qualified as scientific review. In 10 states (38%), institutional review board (IRB) approval could replace scientific review. Twenty-four states (92%) permitted trials without academic medical connection. All states covered privately insured patients; seven (27%) included government and Medicaid patients. Fourteen states (54%) covered phase I to phase IV trials. Sixteen states (62%) covered treatment trials only; one (4%) covered prevention, detection, treatment, and palliation. Thirteen states (50%) covered research-related injuries. Only seven states (27%) required IRB approval. Three states (12%) required commensurate risks and benefits; 23 (88%) had no standard. Eight states (31%) required clinical equipoise with standard care; eight (31%) had no standard; and remaining states (46%) had unique standards. Two states (8%) addressed publication or registries. CONCLUSIONS: Most states did not demand independent scientific review, IRB review, or basic ethical features of high-quality trials; provided partial coverage; omitted prevention, detection, and palliation research; and omitted mandated coverage for research-related injuries. Few required evaluation, independence in publication, or posting trial results. Further research on the impact of diverse state choices would improve policy making.

Multidimensional results reporting to participants in genomic studies: getting it right.

Recent surveys about participation in cohort studies reconfirm that participants value and desire the return of research results to a degree that is out of step with the restrictive recommendations of various ethics advisory groups, which have historically limited disclosure based on clinician value judgments and the severity and treatability of the disease in question, among other factors. Rather than framing the current inconclusive ethics discussion as a standstill among competing ethical principles and their potential applicability, we introduce a new element, communicability (that is, those properties of a message that will determine how likely it is that its informational intent will be grasped by the study participant), as the subject of empirical research to align participants' goals with beneficent and responsible results reporting. Structural changes in research design, combined with governance changes in assessing impact, allow us to move beyond a binary construction of report/do not report and to create a structure in which the communicability of the message and the participants' preferences are variables in a function that affects results reporting. Here we illustrate this structure and its principles.

Patients beware: commercialized stem cell treatments on the web.

A report by the International Society for Stem Cell Research (ISSCR)'s Task Force on Unproven Stem Cell Treatments outlines development of resources for patients, their families, and physicians seeking information on stem cell treatments.

Retroactive ethics in rapidly developing scientific fields.

Science often progresses faster than regulation, and retroactive ethically linked rules have been a persistent issue in stem cell research. Proposed NIH funding rules are retroactive. Legal history and ethical analysis show why there should be a strong presumption that such new rules should be only prospective, in any area of scientific research.