Research Oversight Research Articles

A Changing World in Gene Therapy Research: Exciting Opportunities for Medical Advancement and Biosafety Challenges.

Introduction: We previously reported on the United States' regulatory environment evolving to accommodate an emerging boom in gene therapy research. Several important developments have transpired in the 2 years since that article was published, including the coronavirus disease 2019 (COVID-19) pandemic and the drive for large-scale testing of vaccines containing recombinant or synthetic nucleic acid molecules. This report highlights key developments in the field with a focus on biosafety and issues of note to biosafety professionals with responsibilities over clinical research.Discussion: We provide guidance for performing risk assessments on the currently approved gene therapy products as well as the most utilized types of investigational products in clinical trials. Areas of focus include the prominent approaches utilized in the three major areas of research: oncology, infectious diseases, and rare diseases.Conclusion: The COVID-19 pandemic has created several opportunities for continued growth in gene therapy. National vaccination campaigns will result in greater public acceptance of gene therapy research. Technological advancements that made the vaccine race possible will spur the next generation of research. Advancements born in the developed world set the stage for the creation of therapeutics to treat greater numbers in the developing world and have the potential for massive benefits to global public health. Biosafety professionals and Institutional Biosafety Committees play key roles in contributing to the safe evidence-based advancement of gene therapy research. Biosafety professionals responsible for clinical research oversight must be aware of emerging technologies and their associated risks to support the safe and ethical conduct of research.

A model for the assessment, care, and treatment of suicidal risk within the military intelligence community

ABSTRACT This paper describes the development of a behavioral health and wellness model into the US Army Intelligence and Security Command (INSCOM) to address concerns about suicide within this community. In response to stresses existing within the intelligence community (IC), INSCOM partnered with the Army Public Health Center (APHC) to assess the health and wellbeing of Command personnel. A Community Health Assessment (CHA) survey was conducted (N = 2,704 Soldiers; N = 959 Civilians) that included focus groups across three installations and secondary source data. Six key areas were prioritized: suicide behavior, behavioral health access to care and health promotion, behavioral health stigma and maintaining clearances, workplace environment, sleep health, and overall fitness. Several actions were implemented to address the report’s findings and recommendations. A Command Surgeon office was established within INSCOM. An INSCOM Health Assessment and Readiness Team (I-HART) was established. The Deputy Undersecretary of the Army provided support to address suicide within INSCOM by approving 4 highly qualified experts (HQE’s) in behavioral health and clinical suicidology to provide research oversight and make recommendations. The Command General approved 8 behavioral health providers. There are planned research efforts within the command focusing on scalable and technology enabled care delivery to improve mental well-being and decrease suicides.

Privacy and artificial intelligence: challenges for protecting health information in a new era

BackgroundAdvances in healthcare artificial intelligence (AI) are occurring rapidly and there is a growing discussion about managing its development. Many AI technologies end up owned and controlled by private entities. The nature of the implementation of AI could mean such corporations, clinics and public bodies will have a greater than typical role in obtaining, utilizing and protecting patient health information. This raises privacy issues relating to implementation and data security.Main bodyThe first set of concerns includes access, use and control of patient data in private hands. Some recent public–private partnerships for implementing AI have resulted in poor protection of privacy. As such, there have been calls for greater systemic oversight of big data health research. Appropriate safeguards must be in place to maintain privacy and patient agency. Private custodians of data can be impacted by competing goals and should be structurally encouraged to ensure data protection and to deter alternative use thereof. Another set of concerns relates to the external risk of privacy breaches through AI-driven methods. The ability to deidentify or anonymize patient health data may be compromised or even nullified in light of new algorithms that have successfully reidentified such data. This could increase the risk to patient data under private custodianship.ConclusionsWe are currently in a familiar situation in which regulation and oversight risk falling behind the technologies they govern. Regulation should emphasize patient agency and consent, and should encourage increasingly sophisticated methods of data anonymization and protection.

Best Practices for Conducting Clinical Trials With Indigenous Children in the United States.

We provide guidance for conducting clinical trials with Indigenous children in the United States. We drew on extant literature and our experience to describe 3 best practices for the ethical and effective conduct of clinical trials with Indigenous children. Case examples of pediatric research conducted with American Indian, Alaska Native, and Native Hawaiian communities are provided to illustrate these practices. Ethical and effective clinical trials with Indigenous children require early and sustained community engagement, building capacity for Indigenous research, and supporting community oversight and ownership of research. Effective engagement requires equity, trust, shared interests, and mutual benefit among partners over time. Capacity building should prioritize developing Indigenous researchers. Supporting community oversight and ownership of research means that investigators should plan for data-sharing agreements, return or destruction of data, and multiple regulatory approvals. Indigenous children must be included in clinical trials to reduce health disparities and improve health outcomes in these pediatric populations. Establishment of the Environmental Influences on Child Health Outcomes Institutional Development Award States Pediatric Clinical Trials Network (ECHO ISPCTN) in 2016 creates a unique and timely opportunity to increase Indigenous children's participation in state-of-the-art clinical trials.

Editor's Note: Functional Roles of Src and Fgr in Ovarian Carcinoma.

The editors are publishing this note to alert readers to a concern about [this article][1] ([1][2]): in Fig. 5B, one of the representative Ki67 images was duplicated between the “Control siRNA/CH-NP” and “Src siRNA/CH-NP” groups. MD Anderson's Office of Research Oversight and Integrity

Editor's Note: Therapeutic Targeting of ATP7B in Ovarian Carcinoma.

The editors are publishing this note to alert readers to a concern about [this article][1] ([1][2]): in Fig. 5A, the representative images for “empty liposome” and “control siRNA-DOPC” were both from the “empty liposome” group. MD Anderson's Office of Research Oversight and Integrity

Ethical frameworks in clinical research processes during COVID-19: a scoping review

ObjectivesIn response to the COVID-19 pandemic there have been significant developments in research, its conduct and the supporting ethical framework. While many protocols have been delayed, halted or modified, other...

Human embryo research, stem cell-derived embryo models and invitro gametogenesis: Considerations leading to the revised ISSCR guidelines.

SummaryThe ISSCR Guidelines for Stem Cell Research and Clinical Translation were last revised in 2016. Since then, rapid progress has been made in research areas related to in vitro culture of human embryos, creation of stem cell-based embryo models, and in vitro gametogenesis. Therefore, a working group of international experts was convened to review the oversight process and provide an update to the guidelines. This report captures the discussion and summarizes the major recommendations made by this working group, with a specific emphasis on updating the categories of review and engagement with the specialized scientific and ethical oversight process.

"A cohort of pirate ships": biomedical citizen scientists' attitudes toward ethical oversight.

As biomedical citizen science initiatives become more prevalent, the unique ethical issues that they raise are attracting policy attention. The ethical oversight of bottom-up biomedical citizen science projects that are designed and executed primarily or solely by members of the public is a significant concern because the federal rules that require ethical oversight of research by institutional review boards generally do not apply to such projects, creating what has been called an ethics gap. Working to close this gap, practitioners and scholars have considered new mechanisms of ethical oversight for biomedical citizen science. To date, however, participants' attitudes about ethics and oversight preferences have not been systematically examined. This information is useful to efforts to develop ethical oversight mechanisms because it provides a basis for evaluating the likely effectiveness of specific features of such mechanisms and their acceptability from the perspective of biomedical citizen scientists. Here, we report data from qualitative interviews with 35 stakeholders in bottom-up biomedical citizen science about their general ethics attitudes and preferences regarding ethical oversight. Interviewees described ten ethical priorities and endorsed oversight mechanisms that are voluntary, community-driven, and offer guidance. Conversely, interviewees rejected mechanisms that are mandatory, hierarchical, and inflexible. Applying these findings, we conclude that expert consultation and community review models appear to align well with ethical priorities and oversight preferences of many biomedical citizen scientists, although local conditions should guide the development and use of mechanisms in specific communities.

Who Says Yes or No? Models of Ethical and Safety Oversight for Student-Led Political Violence Research

ABSTRACTThe ethical risks inherent in student research on political violence that involve human participants are myriad. Undergraduate and master’s students face constraints that are different than those for many doctoral students and faculty researchers, and it is the responsibility of educators and academic institutions to ensure that students engage in ethical practices and to mitigate risks. This article focuses on formal mechanisms of oversight. Drawing on discussions with colleagues across the globe, we describe how institutions can design oversight mechanisms to manage student research. We present five distinct models for how ethical oversight of student research is provided in academic programs around the world, considering the costs and benefits of each model. The article concludes that whereas the creation of oversight systems can seem daunting, it is useful to start small—indeed, moving from no oversight to some oversight is a significant improvement. Programs and academic units then can build on these early efforts, experiment with other systems, and eventually develop a system that is adapted to an institution through iterative improvements based on student and faculty experiences.

Challenges to biobanking in LMICs during COVID-19: time to reconceptualise research ethics guidance for pandemics and public health emergencies?

Biobanking can promote valuable health research that may lead to significant societal benefits. However, collecting, storing and sharing human samples and data for research purposes present numerous ethical challenges. These...

A scoping review of genetics and genomics research ethics policies and guidelines for Africa

BackgroundGenetics and genomics research (GGR) is increasingly being conducted around the world; yet, researchers and research oversight entities in many countries have struggled with ethical challenges. A range of ethics and regulatory issues need to be addressed through comprehensive policy frameworks that integrate with local environments. While important efforts have been made to enhance understanding and awareness of ethical dimensions of GGR in Africa, including through the H3Africa initiative, there remains a need for in-depth policy review, at a country-level, to inform and stimulate local policy development and revision on the continent.MethodsTo identify and characterize existing ethics-related guidelines and laws applicable to GGR across much of Africa, we conducted a scoping review of English language policy documents identified through databases, repositories, and web searches. Thirty-six documents were included and coded using a framework that contained a range of themes across five analytical categories: (1) respect, (2) beneficence, (3) justice, (4) independent oversight, and (5) bans and prohibitions. Data analysis software (NVivo 12) was used to organize, code, and tabulate information according to document characteristics and topics. Illustrative examples of policy requirements were selected for inclusion.ResultsDocuments that met inclusion criteria spanned 20 years; published between 1996 and 2018, with the majority (58%) published after 2009. About two-thirds were denoted as “guidelines,” and slightly more than half were non-exclusive to GGR. Very few (six) country-level documents identified were specific to GGR. Requirements related to the principle of “respect” appeared most often across all documents, relative to other principles and processes. The most commonly stated ban was on reproductive cloning. Other prohibitions applied to germline editing, undue inducements in research, sample use for commercial purposes, employee mandatory DNA testing, fetal sex selection, stem cell use, eugenics, and research without public health benefits.ConclusionsEnforceable policies that are indispensable to the ethical conduct and review of GGR are either deficient or missing in many African countries. Existing international, GGR-specific ethics guidelines can be used to inform GGR policy development at a country-level, in conjunction with insight from country specific ethics committees and other local stakeholders.

Governing AI-Driven Health Research: Are IRBs Up to the Task?

Many are calling for concrete mechanisms of oversight for health research involving artificial intelligence (AI). In response, institutional review boards (IRBs) are being turned to as a familiar model of governance. Here, we examine the IRB model as a form of ethics oversight for health research that uses AI. We consider the model's origins, analyze the challenges IRBs are facing in the contexts of both industry and academia, and offer concrete recommendations for how these committees might be adapted in order to provide an effective mechanism of oversight for health-related AI research.

Ethical Oversight of Implementation Research in Rural Settings of a Developing Country During the COVID-19 Outbreak.

Ethical Oversight of Implementation Research in Rural Settings of a Developing Country During the COVID-19 Outbreak.

Comparison of Knowledge, Attitude, Anxiety, and Behaviours in Medical and Non-medical Students Towards COVID-19 Vaccination: A Need for Concern Amidst the Pandemic

Purpose: COVID-19, a pandemic declared on March 11th, 2020, makes it crucial for the whole world to control and ensure safety measures to control such infections in the future. Fear, worry, and panic remain widespread, especially among healthcare workers. We aimed to compare the knowledge, attitude, anxiety, and behaviours of medical and non-medical students towards vaccination against COVID-19. Material and Methods: We conducted a cross-sectional study for one month on the MBBS/BDS and undergraduate nonmedical students through an online questionnaire which consisted of a multiple choice KAP questionnaire consisting of four sections (i.e., socio-demographic details, knowledge, attitudes, and behavior). Multiple linear regression was performed to determine the variables predicting knowledge and attitudes towards COVID-19 vaccination. Results: Vaccine hesitancy was detected in 17% of Undergraduate Medical Students, while the same was noted in 45% of non-medical students. 48.7% of medical students knew about different vaccines available in India for COVID-19 viz a viz the same in non-medical students was 49.5%. The majority of the students (35.8% medical and 48.6% non-medical) considered Covishield the best currently available vaccine in India. The majority of the students (Medical 86.5% and non-medical 75.2%) thought that the COVID-19 vaccine could reduce the spread of the disease in the community. In the multiple regression model, better socioeconomic status, holding nuclear families, and having a history of essential vaccinations uptake were linked with knowledge, while attitudes were substantially associated with being female and having a previous history of vital vaccines uptake. Conclusion: The results showed that medical students had sufficient knowledge, an optimistic attitude, and moderate levels of concern towards COVID-19. Vaccine hesitancy was much less among medical when compared to non-medical students. Expanding knowledge and regulatory oversight of vaccine research and the public release of safety data may lessen vaccine reluctance among students.

Evaluating the National Institutes of Health's Sex as a Biological Variable Policy: Conflicting Accounts from the Front Lines of Animal Research.

Background: Since the National Institutes of Health (NIH) Revitalization Act of 1993, focus on the equitable inclusion of women in clinical research has been ongoing. NIH's 2015 sex as a biological variable (SABV) policy aims to transform research design, analysis, and reporting in the preclinical sphere by including male and female organisms in vertebrate animal research as well as human studies. However, questions remain regarding how researchers and members of research oversight committees perceive the value and need of the SABV policy.Materials and Methods: Based on 62 interviews with animal researchers and oversight personnel, we analyze what the animal research community knows about the policy and sees as the benefits and challenges of implementation.Results: We found that the 62 interviewees disagreed about the need for the policy, with some being supportive and others questioning whether the policy is based on science or is politically motivated. There were also tensions in how interviewees conceptualized the challenges to and resources needed for implementing the SABV policy. For instance, while some thought implementation would require a significant increase in numbers of animals used for each study, others explicitly rejected this claim.Conclusions: We conclude by discussing the practical and social implications of our findings about the views of members of the animal research community regarding the SABV policy.

Core components and strategies for suicide and risk management protocols in mental health research: a scoping review

BackgroundSuicide and risk management protocols in mental health research aim to ensure patient safety, provide vital information on how to assess suicidal ideation, manage risk, and respond to unexpected and expected situations. However, there is a lack of literature that identifies specific components and strategies to include in suicide and risk management protocols (SRMPs) for mental health research. The goal of this scoping review was to review academic and grey literature to determine core components and associated strategies, which can be used to inform SRMPs in mental health research.Methods and analysisThe methodological framework outlined by Arksey and O’Malley was used for this scoping review. The search strategy, conducted by a medical librarian, was multidisciplinary and included seven databases. Two reviewers independently assessed eligibility criteria in each document and used a standardized charting form to extract relevant data. The extracted data were then examined using qualitative content analysis. Specifically, summative content analysis was used to identify the core components and strategies used in SRMPs. The data synthesis process was iterative.ResultsThis review included 36 documents, specifically 22 peer-reviewed articles and 14 documents from the grey literature. Five core components of SRMPs emerged from the reviewed literature including: training; educational resources for research staff; educational resources for research participants; risk assessment and management strategies; and clinical and research oversight. Potentials strategies for risk mitigation within each of the core components are outlined.ConclusionsThe five core components and associated strategies for inclusion in SRMPs will assist mental health researchers in conducting research safely and rigorously. Findings can inform the development of SRMPs and how to tailor them across various research contexts.

Ethically Justified, Practical Guidance for the Professionally Responsible Investigation of Maternal-Fetal Intervention for Fetal or Neonatal Benefit

Abstract This paper provides ethical guidance for the professionally responsible clinical investigation of maternal-fetal investigation for fetal or neonatal benefit and its transition into clinical practice. We present an ethical framework based on the ethical principles of beneficence, respect for autonomy, and justice, the professional virtue of integrity, and the ethical concept of the fetus as a patient. We identify the implications of this ethical framework for the qualifications that centers for maternal-fetal intervention should satisfy. These centers have the ethical obligation to provide prospective review and oversight of both innovation (an experiment undertaken to benefit an individual patient) and research (an experiment undertaken to create generalizable knowledge). We describe ethically justified criteria for innovation and early-phase research, for randomized clinical trials, and for the responsible transition into clinical practice. We also identify the elements of the informed consent process, including measures to prevent therapeutic misconception by pregnant patients during the informed consent process. The scientific, clinical, and ethical requirements of maternal-fetal investigation are demanding. However, the commitment to safety and quality requires that they be met. Fulfilling this commitment will result in well-documented professionally responsible investigation of maternal-fetal intervention for fetal and neonatal benefit.

Editors' Note.

Editors' Note James M. DuBois, Ana S. Iltis, and Heidi A. Walsh Shortly after the March 2020 COVID-19 stay-at-home orders, the Bioethics Research Center (BRC) at Washington University, directed by NIB co-editor James DuBois, submitted a grant proposal for a project "Innovative Medicine and Research on COVID-19: Addressing Potential Ethical, Oversight, and Regulatory Barriers." The project was supported by the NIH, National Institute on Aging (NIA) [3R01AG058254–03S1] and aimed to conduct an online survey with IRB professionals or researchers who review, propose, or conduct research on COVID-19. The goal was to better understand the ethical, oversight, and regulatory barriers of doing COVID-related research during the pandemic. The survey included a question that asked participants if they would be willing to share more about their experience in a narrative published in NIB. The symposium editors invited authors to share their experiences in this double issue of NIB, comprised of personal stories from 12 IRB professionals and 12 COVID-19 researchers. An additional 4 narratives from IRB professionals and 5 from researchers are included in the online supplement. The narratives offer lessons on how regulations and institutional policies and practices can be modified to accommodate the needs of researchers and society during pandemics. The narratives also serve as an historical account of research and research oversight during this unique and extraordinary time. Ana Iltis and Gianna McMillan served as the narrative symposium editors. The two, along with the editorial office, wrote a call for stories that was sent to researchers and IRB professionals along with an invitation to write and share their stories. Gianna McMillan, Jerry Menikoff, and Sumit Mohan contributed commentaries on the IRB professionals' narratives, while Ana Iltis, Bruce Gordon, and J. Wilson Jackson provided commentary on the researcher narratives. The commentary authors offer their perspectives on the narratives through the lens of their expertise in research ethics, health law and policy, medical research, and patient and research subject advocacy. "Asking the simple question 'What does love require of me?' when faced with a difficult decision might open up ways of thinking and acting that otherwise may not have come to mind." Sams et al. contributed the research article in this issue of NIB, "The Secret of Quality Is Love: A Qualitative Study Exploring Physician and Nurse Perspectives on What It Means to Love Their Patients." The authors hypothesized that "there is a language of love relevant to health care, which can inform its practice and shape future healthcare professionals." The authors conducted in-depth interviews with 29 physicians and 32 nurses to explore their perspectives on what it means to love their patients. Participants expressed specific hallmarks and virtues that they believe characterize loving physicians and nurses. Practical examples include providing excellent care, advocating for patients, ensuring patients are comfortable, and listening to patients. The majority of participants contended that loving their patients may be the secret to providing high-quality health care. This issue of NIB includes two case studies. The first, "The Ethics of Choosing a Surrogate Decision [End Page vii] Maker When Equal-Priority Surrogates Disagree" is from our case study partnership with the UCLA Health Ethics Center. The author, Matthew Shea, discusses how to proceed when surrogate decision makers of equal priority disagree—a relatively common dilemma on which there is no ethical consensus. In this case, an elderly female had suffered a stroke and was not capable of medical decision making. Her four adult children disagreed on whether to continue aggressive treatments or transition her to comfort care and allow her to die. Three of the children favored comfort care, while one argued for continued treatment. Shea proposes three methods for choosing a surrogate in cases of disagreement. The second case study in this issue "A Gay Epidemiologist and the DC Commission of Public Health AIDS Advisory Committee," by Steven Coughlin, Paul Mann and Bruce Jennings is based upon lead author, epidemiologist Steven Coughlin's experience on an AIDS Advisory Committee in DC in the 1990s. Coughlin served on the committee at a time when AIDS was also a common and tragic theme in his private life and social circle. In creating and distributing educational materials...

Rethinking Human Embryo Research Policies.

It now seems technically feasible to culture human embryos beyond the “fourteen‐day limit,” which has the potential to increase scientific understanding of human development and perhaps improve infertility treatments. The fourteen‐day limit was adopted as a compromise but subsequently has been considered an ethical line. Does it remain relevant in light of technological advances permitting embryo maturation beyond it? Should it be changed and, if so, how and why? What justifications would be necessary to expand the limit, particularly given that doing so would violate some people's moral commitments regarding human embryos? Robust stakeholder engagement preceded adoption of the fourteen‐day limit and should arguably be part of efforts to reassess it. Such engagement could also consider the need for enhanced oversight of human embryo research. In the meantime, developing and implementing reliable oversight systems should help foster high‐quality research and public confidence in it.