The bench is closer to the bedside than we think: Uncovering the ethical ties between preclinical researchers in translational neuroscience and patients in clinical trials.

Millions of people worldwide currently suffer from serious neurological diseases and injuries for which there are few, and often no, effective treatments. The paucity of effective interventions is, no doubt, due in large part to the complexity of the disorders, as well as our currently limited understanding of their pathophysiology. The bleak picture for patients, however, is also attributable to avoidable impediments stemming from quality concerns in preclinical research that often escape detection by research regulation efforts. In our essay, we connect the dots between these concerns about the quality of preclinical research and their potential ethical impact on the patients who volunteer for early trials of interventions informed by it. We do so in hopes that a greater appreciation among preclinical researchers of these serious ethical consequences can lead to a greater commitment within the research community to adopt widely available tools and measures that can help to improve the quality of research.

Do we really know how many clinical trials are conducted ethically? Why research ethics committee review practices need to be strengthened and initial steps we could take to strengthen them.

Research Ethics Committees (RECs) play a critical gatekeeping role in clinical trials. This role is meant to ensure that only those trials that meet certain ethical thresholds proceed through their gate. Two of these thresholds are that the potential benefits of trials are reasonable in relation to risks and that trials are capable of producing a requisite amount of social value. While one ought not expect perfect execution by RECs of their gatekeeping role, one should expect routine success in it. This article reviews a range of evidence showing that substantial numbers of ethically tainted trials are receiving REC approvals. Many of the trials are early phase trials that evidence shows have benefits that may not be reasonable compared with their risks and many others are later trials that evidence shows may lack sufficient social value. The evidence pertains to such matters as methodologically inadequate preclinical studies incapable of supporting the inferences that REC members must make about the prospects for potential benefit needed to offset the risks in early phase trials and sponsorship bias that can cause improperly designed, conducted, analysed and reported later phase trials. The analysis of the evidence makes clear that REC practices need to be strengthened if they are to adequately fulfil their gatekeeping role. The article also explores options that RECs could use in order to improve their gatekeeping function.

Rescuing Informed Consent: How the new "Key Information" and "Reasonable Person" Provisions in the Revised U.S. Common Rule open the door to long Overdue Informed Consent Disclosure Improvements and why we need to walk Through that door.

There is substantial published evidence showing that countless people enroll each year in ethically deficient clinical trials. Many of the trials are problematic because the quality of the science used to justify their launch may not be sufficiently vetted while many other trials may lack requisite social value. This poses the question: why do people volunteer for them? The answer resides in large part in the fact that informed consent practices have historically masked, rather than disclosed, the information that would alert research candidates to the ethically problematic nature of the trials. The "reasonable person" and "key information" provisions in the revised US Common Rule create the opportunity to correct this historical shortcoming. Two sources are employed to shed light on what the "key information" is that should be disclosed to a "reasonable person": the original disclosure aims of the Nuremberg Code, as well as an extensive body of meta-research evidence. Those sources jointly support a range of new disclosures in the informed consent process that would unmask the heretofore undisclosed information. The resulting proposed new disclosures pertain to the overall success prospects of clinical trials, the quality of the prior research that both forms the basis of clinical trials and informs assessment of their risks and benefits, the potential social value of clinical trials, and the commercial purposes of clinical trials.

Marketing the Research Missions of Academic Medical Centers: Why Messages Blurring Lines Between Clinical Care and Research Are Bad for both Business and Ethics.

Academic Medical Centers (AMCs) offer patient care and perform research. Increasingly, AMCs advertise to the public in order to garner income that can support these dual missions. In what follows, we raise concerns about the ways that advertising blurs important distinctions between them. Such blurring is detrimental to AMC efforts to fulfill critically important ethical responsibilities pertaining both to science communication and clinical research, because marketing campaigns can employ hype that weakens research integrity and contributes to therapeutic misconception and misestimation, undermining the informed consent process that is essential to the ethical conduct of research. We offer ethical analysis of common advertising practices that justify these concerns. We also suggest the need for a deliberative body convened by the Association of American Medical Colleges and others to develop a set of voluntary guidelines that AMCs can use to avoid in the future, the problems found in many current AMC advertising practices.

Taking steps to increase the trustworthiness of scientific research.

To enjoy the public's trust, the research community must first be clear about what it is expected to do and then avoid the incidents that prevent it from meeting those expectations. Among other things, there are expectations that published scientific results will be reliable, that research has the potential to contribute to the common good, and that research will be conducted ethically. Consequently, the scientific community needs to avoid lapses that prevent it from meeting these three expectations. This requires a strong commitment to trustworthy research practices, as well as mechanisms that diminish lapses that inevitably occur in complex endeavors such as scientific research. The author presents a model to assess the strength of commitment to trustworthy research and explores proven quality assurance mechanisms that can diminish lapses in research injurious to the public's trust. Some mechanisms identify in advance ways that things can go wrong so that steps can be taken to prevent them from going wrong in the first place. Other mechanisms investigate past errors or near misses to discover their causes so that they can be addressed to avoid similar future instances. The author explains why such methods are useful to efforts to promote research worthy of the public's trust.

"Editing" Genes: A Case Study About How Language Matters in Bioethics.

Metaphors used to describe new technologies mediate public understanding of the innovations. Analyzing the linguistic, rhetorical, and affective aspects of these metaphors opens the range of issues available for bioethical scrutiny and increases public accountability. This article shows how such a multidisciplinary approach can be useful by looking at a set of texts about one issue, the use of a newly developed technique for genetic modification, CRISPRcas9.

Building research capacity with members of underserved American Indian/Alaskan Native communities: training in research ethics and the protection of human subjects.

OBJECTIVE: To develop a research ethics training course for American Indian/Alaskan Native health clinic staff and community researchers who would be conducting human subjects research. METHOD: Community-based participatory research methods were used in facilitated discussions of research ethics centered around topics included in the Collaborative Institutional Training Initiative research ethics course. RESULTS: The community-based participatory research approach allowed all partners to jointly develop a research ethics training program that was relevant for American Indian/Alaskan Native communities. All community and clinic partners were able to pass the Collaborative Institutional Training Initiative course they were required to pass so that they could be certified to conduct research with human subjects on federally funded projects. In addition, the training sessions provided a foundation for increased community oversight of research. CONCLUSIONS: By using a collaborative process to engage community partners in research ethics discussions, rather than either an asynchronous online or a lecture/presentation format, resulted in significant mutual learning about research ethics and community concerns about research. This approach requires university researchers to invest time in learning about the communities in which they will be working prior to the training.

Eliminating LGBTIQQ Health Disparities: The Associated Roles of Electronic Health Records and Institutional Culture.

For all humans, sexual orientation and gender identity are essential elements of identity, informing how we plan and live our lives. The historic invisibility of sexual minorities in medicine has meant that these important aspects of their identities as patients have been ignored, with the result that these patients have been denied respect, culturally competent services, and proper treatment. Likely due to historic rejection and mistreatment, there is evidence of reluctance on the part of LGBT patients to disclose their sexual orientation (SO) or gender identity (GI) to their health care providers. There is some perception of risk in sharing SO and GI for many patients who have had bad prior experiences. Despite these risks, we argue that we can improve the quality of care provided this population only by encouraging them to self-identify and then using that information to improve quality of care. One strategy both to prompt patient self-identification and to store and use SO and GI data to improve care centers on the use of electronic health records. However, gathering SO and GI data in the EHR requires a workforce that knows both how to obtain and how to use that information. To develop these competencies, educational programs for health professionals must prepare students and educators to elicit and to use sexual orientation and gender identity information to improve care while simultaneously ensuring the safety of patients, trainees, and staff and faculty members as SO and GI become openly discussed and integral parts of ongoing medical discussion and care. As determination of SO and GI demographics becomes more common in health research, we will more fully understand the health risks for all the LGBTIQQ populations.

Newborn screening and cascade testing for FMR1 mutations.

We describe an ongoing pilot project in which newborn screening (NBS) for FMR1 mutations and subsequent cascade testing are performed by the MIND Institute at the University of California, Davis Medical Center (UCDMC). To date, out of 3,042 newborns initially screened, 44 extended family members have been screened by cascade testing of extended family members once a newborn is identified. Fourteen newborns (7 males and 7 females) and 27 extended family members (5 males and 22 females) have been identified with FMR1 mutations. Three family histories are discussed in detail, each demonstrating some benefits and risks of NBS and cascade testing for FMR1 mutations in extended family members. While we acknowledge inherent risks, we propose that with genetic counseling, clinical follow-up of identified individuals and cascade testing, NBS has significant benefits. Treatment for individuals in the extended family who would otherwise not have received treatment can be beneficial. In addition, knowledge of carrier status can lead to lifestyle changes and prophylactic interventions that are likely to reduce the risk of late onset neurological or psychiatric problems in carriers. Also with identification of carrier family members through NBS, reproductive choices become available to those who would not have known that they were at risk to have offspring with fragile X syndrome.

Using the concept of "deserved trust" to strengthen the value and integrity of biomedical research.

It is commonplace for science leaders and others to claim that the future of biomedical research rests in large part upon the public's trust. If true, it behooves the biomedical research community to understand how it avoids taking chances with that trust. This commentary, which builds upon comments of noted trust scholar Russell Hardin about how best to enjoy trust, assumes that the key to being trusted is deserving to be trusted. Thus, it proposes using "deserved trust" to identify ways that the public's trust in biomedical research could be better supported. Employing deserved trust to support the public's trust leads us to consider what it is that the biomedical research community should be trusted to do, examine the evidence about the effectiveness of current safeguards meant to assure that those things routinely get done, and identify new ways to equip individual researchers, research teams, and research institutions to assure that the public's trust in their research is deserved rather than misplaced.

Public trust and research a decade later: what have we learned since Jesse Gelsinger's death?

Almost a decade has passed since the untimely death of Jesse Gelsinger. The reflections of Dr. Wilson and efforts made on a national scale to address various ethical issues in biomedical research provide an opportunity to consider what progress has been made in efforts to build and restore the public's trust in biomedical research. The restoration of public trust is especially critical in the aftermath of tragic events like Mr. Gelsinger's death and the authors note the need for greater emphasis on building public trust than has occurred to date in the broader biomedical research community.

Twentieth-century science education and 21st-century genetic engineering technologies: A toxic mix.

I challenge the "convenient consensus" that He Jiankui is a "bad apple" in order to consider alternative explanations for why He may have ventured down the ill-considered path in his research that he did. The answer I want to proffer is that He was ill-equipped by his education and training in biomedical research to appropriately weigh the competing goods he encountered and thus was not able to be swayed by the clear guidance that basic ethical considerations would have provided. If true, this shows us why, much as we would like to take solace in him being a bad apple, we should be prompted by this episode to focus instead on systems level contributors to He's decisions that, if left unaddressed, will surely lead to similarly reckless episodes by other researchers in the future.

Four erroneous beliefs thwarting more trustworthy research.

A range of problems currently undermines public trust in biomedical research. We discuss four erroneous beliefs that may prevent the biomedical research community from recognizing the need to focus on deserving this trust, and thus which act as powerful barriers to necessary improvements in the research process.

Recommendations for Effective Integration of Ethics and Responsible Conduct of Research (E/RCR) Education into Course-Based Undergraduate Research Experiences: A Meeting Report.

Advancement of the scientific enterprise relies on individuals conducting research in an ethical and responsible manner. Educating emergent scholars in the principles of ethics/responsible conduct of research (E/RCR) is therefore critical to ensuring such advancement. The recent impetus to include authentic research opportunities as part of the undergraduate curriculum, via course-based undergraduate research experiences (CUREs), has been shown to increase cognitive and noncognitive student outcomes. Because of these important benefits, CUREs are becoming more common and often constitute the first research experience for many students. However, despite the importance of E/RCR in the research process, we know of few efforts to incorporate E/RCR education into CUREs. The Ethics Network for Course-based Opportunities in Undergraduate Research (ENCOUR) was created to address this concern and promote the integration of E/RCR within CUREs in the biological sciences and related disciplines. During the inaugural ENCOUR meeting, a four-pronged approach was used to develop guidelines for the effective integration of E/RCR in CUREs. This approach included: 1) defining appropriate student learning objectives; 2) identifying relevant curriculum; 3) identifying relevant assessments; and 4) defining key aspects of professional development for CURE facilitators. Meeting outcomes, including the aforementioned E/RCR guidelines, are described herein.