Alan Regenberg

Psychiatric and neuropsychiatric adverse events associated with deep brain stimulation: A meta-analysis of ten years' experience

Deep brain stimulation (DBS) has been approved by the FDA for use in the treatment of Parkinsons disease, essential tremor, and dystonia. Case reports and case series have reported significant psychiatric side effects in some individuals. The goal of this meta‐analysis is to characterize the risks and benefits of DBS and to assess its possible use within the psychiatric setting. A search was conducted on PubMed, EBSCO, and PsycInfo in January 2006 that covered the time period 1 Jan 1996–30 Dec 2005. All identified articles were reviewed and those describing adverse events were further examined with a structured instrument. The initial searches yielded 2667 citations; 808 articles met inclusion criteria for the meta‐analysis; 98.2% of studies that specifically assessed motor function reported some level of improvement. Most reported side effects were device or procedure related (e.g., infection and lead fracture). The prevalence of depression was 2–4%, mania 0.9–1.7%, emotional changes 0.1–0.2%, and the prevalence of suicidal ideation/suicide attempt was 0.3–0.7%. The completed suicide rate was 0.16–0.32%. In conclusion, DBS is an effective treatment for Parkinsons disease, dystonia, and essential tremor, and case reports suggest that major depression and OCD may also respond to DBS. Reported rates of depression, cognitive impairment, mania, and behavior change are low, but there is a high rate of suicide in patients treated with DBS, particularly with thalamic and GPi stimulation. Because of the high suicide rate, patients should be prescreened for suicide risk prior to DBS surgery. Additionally, patients should be monitored closely for suicidal behavior post‐operatively.

Medicine on the Fringe: Stem Cell-Based Interventions in Advance of Evidence

Stem cell‐based interventions (SCBIs) offer great promise; however, there is currently little internationally accepted, scientific evidence supporting the clinical use of SCBIs. The consensus within the scientific community is that a number of hurdles still need to be cleared. Despite this, SCBIs are currently being offered to patients. This article provides a content analysis of materials obtained from SCBI providers. We find content that strains credulity and almost no evidence of SCBIs being delivered in the context of clinical trials. We conclude that until scientific evidence is available, as a general rule, providers should only offer SCBIs in the context of controlled clinical trials. Clients should be aware that the risks and benefits of SCBIs are unknown, that their participation is unlikely to advance scientific knowledge, and they are likely to become ineligible to participate in future clinical trials of SCBIs. We recommend steps to promote patient education and enhance global oversight. STEM CELLS 2009;27:2312–2319

CELL-BASED INTERVENTIONS FOR NEUROLOGIC CONDITIONS: ETHICAL CHALLENGES FOR EARLY HUMAN TRIALS

Background: Attempts to translate basic stem cell research into treatments for neurologic diseases and injury are well under way. With a clinical trial for one such treatment approved and in progress in the United States, and additional proposals under review, we must begin to address the ethical issues raised by such early forays into human clinical trials for cell-based interventions for neurologic conditions. Methods: An interdisciplinary working group composed of experts in neuroscience, cell biology, bioethics, law, and transplantation, along with leading disease researchers, was convened twice over 2 years to identify and deliberate on the scientific and ethical issues raised by the transition from preclinical to clinical research of cell-based interventions for neurologic conditions. Results: While the relevant ethical issues are in many respects standard challenges of human subjects research, they are heightened in complexity by the novelty of the science, the focus on the CNS, and the political climate in which the science is proceeding. Conclusions: Distinctive challenges confronting US scientists, administrators, institutional review boards, stem cell research oversight committees, and others who will need to make decisions about work involving stem cells and their derivatives and evaluate the ethics of early human trials include evaluating the risks, safety, and benefits of these trials, determining and evaluating cell line provenance, and determining inclusion criteria, informed consent, and the ethics of conducting early human trials in the public spotlight. Further study and deliberation by stakeholders is required to move toward professional and institutional policies and practices governing this research.

The role of animal models in evaluating reasonable safety and efficacy for human trials of cell-based interventions for neurologic conditions.

Progress in regenerative medicine seems likely to produce new treatments for neurologic conditions that use human cells as therapeutic agents; at least one trial for such an intervention is already under way. The development of cell-based interventions for neurologic conditions (CBI-NCs) will likely include preclinical studies using animals as models for humans with conditions of interest. This paper explores predictive validity challenges and the proper role for animal models in developing CBI-NCs. In spite of limitations, animal models are and will remain an essential tool for gathering data in advance of first-in-human clinical trials. The goal of this paper is to provide a realistic lens for viewing the role of animal models in the context of CBI-NCs and to provide recommendations for moving forward through this challenging terrain.

Genome Editing Technologies and Human Germline Genetic Modification: The Hinxton Group Consensus Statement

To cite this article: Sarah Chan, Peter J. Donovan, Thomas Douglas, Christopher Gyngell, John Harris, Robin Lovell-Badge, Debra J. H. Mathews, Alan Regenberg & On Behalf of the Hinxton Group (2015) Genome Editing Technologies and Human Germline Genetic Modification: The Hinxton Group Consensus Statement, The American Journal of Bioethics, 15:12, 42-47, DOI: 10.1080/15265161.2015.1103814 To link to this article: http://dx.doi.org/10.1080/15265161.2015.1103814

CRISPR: A path through the thicket

As various advisory bodies, scientific organizations and funding agencies deliberate on genome editing in humans, Debra J. H. Mathews, Robin Lovell-Badge and colleagues lay out some key points for consideration.

Resisting the Tide of Professionalization: Valuing Diversity in Bioethics

Robert Baker (2005) argues that professional “codes are aggregative enterprises growing within fields in response to their historical experiences and needs,” and that “the field of bioethics has reached the point at which it has need to assert its integrity and its independence.” The drafting of professional codes and standards represents an important milestone in the ongoing professionalization of bioethics. While Baker’s draft document contributes to the important conversation about this process, there are significant issues associated with professionalization that are not raised in his article. One of the primary reasons to be concerned about professionalization is the risk that it will discourage, quiet, and marginalize important voices that should be included in the discussion, debate, and analysis that characterizes the practice of bioethics. Rather than a conversation about professional codes, our focus should be on developing methods for enhancing diversity as a means to prevent this marginalization. The professionalization of Western medicine, particularly over the past century or so, provides a useful example for this sort of marginalization of alternative views. Rival approaches such as homeopathic, osteopathic, naturopathic and chiropractic medicine languished and almost perished at the hands of the dominant allopathic or evidencebased/disease-focused model that has flourished in western medicine (Baer 1989; Waddington 1990). While many of these alternatives to allopathic medicine still exist, (recent trends may even suggest a minor renaissance for alternative medicines) they are still explicitly complementary and alternative to ‘real’ medicine, rather than legitimate medicine in their own right. Practitioners of complementary and alternative medicine (CAM), in many cases, have now adopted techniques of the dominant allopathic model. In a sense, CAM practices survive as watered down versions of the originals that are now being co-opted by dominant western medicine (Clarke et al. 2004; Kelner et al. 2004; Villanueva-Russell 2005). Our point here is not to question the wisdom of diversification within western medicine or to compare the merits of competing medical models, but instead to draw attention to the marginalization of rivals that accompanied professionalization of medicine, and to offer it as a cautionary tale for bioethicists as they travel down a similar path. As in medicine, mainstream bioethics alone does not capture the full breadth and depth of existing practice. For any specific issue in bioethics, one can identify a range of individuals and groups with vested interest and an arguable stake in the outcome of the related bioethical debate and analysis. While it is perhaps futile to attempt to assemble the full list of stakeholders for a given issue, it is not unreasonable to expect a good faith effort to identify and include a wide range of identifiable stakeholders. Some stakeholders have already managed to insinuate themselves into the practice of bioethics, such as it is, as practitioners of what may be termed outsider bioethics (think outsider art); examples include disease advocacy groups, political groups, and individual activists. Continuing professionalization, in the absence of sincere efforts to be maximally inclusive, is likely to result in the dominance of academic bioethicists over rival stakeholders, many of whom may not even define their activities as ‘bioethics.’ Why should this concern us? The ascendancy of any one group of bioethicists should concern us for the simple reason that there is no dominant universal moral theory available to serve as a gold standard for ethical decision-making—no handy moral machinery into which problems can be entered and from which solutions will emerge. In other words, academic bioethicists have no unique access to the truth or to ‘right’ solutions. While academic bioethicists may not have unique access to truth, they do have access to resources which can allow for the enrichment of bioethics through the enhancement of stakeholder diversity. A commitment to inclusivity is not equivalent to an endorsement of relativism: there are ‘correct’ ethical analyses for any given problem— the challenge is identifying the best answers. Inviting diverse stakeholders to participate as equals does not imply that you are asking a large group to vote on what is right; rather, you are facilitating an opportunity for members of a broad stakeholder group to educate each other about the range of responses that exist in the identified community. Whether debate can lead to compromise or consensus is not nearly as important as the fact that any solution should be proactively tailored to succeed in a context where these competing views exist. Great care should be taken not to allow stakeholder voices to be marginalized as somehow outside of the profession and thus illegitimate. It is fine to disagree with the content of their argument—but completely dismissing those delivering the argument will not settle the debate or advance bioethics.

Bioethical considerations in developing a biorepository for the Pneumonia Etiology Research for Child Health project.

The Pneumonia Etiology Research for Child Health (PERCH) project has the potential to provide a highly valuable resource of biospecimens that may be used to inform future studies on the causes of pneumonia. Designing a biorepository for this complex project was done in collaboration with a wide range of experts including bioethicists. In this paper, we describe the most significant ethical issues encountered related to the biorepository, focusing on its structure and informed consent. We also outline the proposed approach to the PERCH biorepository, which was designed to be sensitive to the ethical, practical, and cultural challenges inherent to the study. Through this process, we concluded that biorepository governance plans and strategies for managing informed consent should be implemented in a way to allow for careful study in order to better understand the attitudes of and impact on the stakeholders involved in the study.

Scarce Resource Allocation During Disasters: A Mixed-Method Community Engagement Study

Background During a catastrophe, health‐care providers may face difficult questions regarding who will receive limited life‐saving resources. The ethical principles that should guide decision‐making have been considered by expert panels but have not been well explored with the public or front‐line clinicians. The objective of this study was to characterize the public’s values regarding how scarce mechanical ventilators should be allocated during an influenza pandemic, with the ultimate goal of informing a statewide scare resource allocation framework. Methods Adopting deliberative democracy practices, we conducted 15 half‐day community engagement forums with the general public and health‐related professionals. Small group discussions of six potential guiding ethical principles were led by trained facilitators. The forums consisted exclusively of either members of the general public or health‐related or disaster response professionals and were convened in a variety of meeting places across the state of Maryland. Primary data sources were predeliberation and postdeliberation surveys and the notes from small group deliberations compiled by trained note takers. Results Three hundred twenty‐four individuals participated in 15 forums. Participants indicated a preference for prioritizing short‐term and long‐term survival, but they indicated that these should not be the only factors driving decision‐making during a crisis. Qualitative analysis identified 10 major themes that emerged. Many, but not all, themes were consistent with previously issued recommendations. The most important difference related to withholding vs withdrawing ventilator support. Conclusions The values expressed by the public and front‐line clinicians sometimes diverge from expert guidance in important ways. Awareness of these differences should inform policy making.

Too Many Patients…A Framework to Guide Statewide Allocation of Scarce Mechanical Ventilation During Disasters

&NA; The threat of a catastrophic public health emergency causing life‐threatening illness or injury on a massive scale has prompted extensive federal, state, and local preparedness efforts. Modeling studies suggest that an influenza pandemic similar to that of 1918 would require ICU and mechanical ventilation capacity that is significantly greater than what is available. Several groups have published recommendations for allocating life‐support measures during a public health emergency. Because there are multiple ethically permissible approaches to allocating scarce life‐sustaining resources and because the public will bear the consequences of these decisions, knowledge of public perspectives and moral points of reference on these issues is critical. Here we describe a critical care disaster resource allocation framework developed following a statewide community engagement process in Maryland. It is intended to assist hospitals and public health agencies in their independent and coordinated response to an officially declared catastrophic health emergency in which demand for mechanical ventilators exceeds the capabilities of all surge response efforts and in which there has been an executive order to implement scarce resource allocation procedures. The framework, built on a basic scoring system with modifications for specific considerations, also creates an opportunity for the legal community to review existing laws and liability protections in light of a specific disaster response process.