Facilitating collaborative animal research: The development and implementation of a Master Reciprocal Institutional Agreement for Animal Care and Use.

Ensuring appropriate review, approval, and oversight of research involving animals becomes increasingly complex when researchers collaborate across multiple sites. In these situations, it is important that the division of responsibilities is clear and that all involved parties share a common understanding. The National Institutes of Health Office of Laboratory Animal Welfare and the United States Department of Agriculture Animal Plant Health Inspection Service require an Institutional Animal Care and Use Committee (IACUC) to review the care and use of animals in research, and both agree that it is acceptable for one IACUC to review the work taking place at multiple institutions. With this in mind, several Harvard-affiliated hospitals and academic centers developed the Master Reciprocal Institutional Agreement for Animal Care and Use (Master IACUC Agreement) to support collaboration, decrease administrative burden, increase efficiencies, reduce duplicative efforts, and ensure appropriate protections for animals used in research. Locally, the Master IACUC Agreement has fostered greater collaboration and exchange while ensuring appropriate review and oversight of research involving animals. As multisite animal protocols become more prevalent, this Agreement could provide a model for a distributed, national network of IACUC reliance.

The SMART IRB platform: A national resource for IRB review for multisite studies.

Single institutional review board (IRB) review of multisite research increased in frequency over a decade ago with a proliferation of master IRB reliance agreements supporting statewide and regional consortia and disease- and population-specific networks. Although successful, the increasing number of agreements presented significant challenges and illuminated potential benefits of a single, nationwide agreement. Anticipated changes in federal regulations highlighted the need to systematize and simplify IRB reliance. To address these challenges, the NIH National Center for Advancing Translational Sciences funded a project to establish a national IRB reliance network that would support national adoption of single IRB (sIRB) review. The Streamlined, Multisite, Accelerated Resources for Trials (SMART) IRB Platform launched in July 2016 to facilitate dissemination, adoption, and implementation of a collaboratively developed master IRB reliance agreement and supportive tools and resources. More than 580 institutions have joined SMART IRB's Master Common Reciprocal Institutional Review Board Authorization Agreement and begun using the SMART IRB platform to support sIRB arrangements. Here, we describe the tenets of the agreement and operational benefits and challenges of its use. SMART IRB's early success affirms the utility of collaborative, flexible, and centralized approaches to supporting sIRB review while highlighting the need for further national harmonization.

Ethical challenges experienced by clinical research nurses:: A qualitative study.

BACKGROUND:: Clinical investigation is a growing field employing increasing numbers of nurses. This has created a new specialty practice defined by aspects unique to nursing in a clinical research context: the objectives (to implement research protocols and advance science), setting (research facilities), and nature of the nurse-participant relationship. The clinical research nurse role may give rise to feelings of ethical conflict between aspects of protocol implementation and the duty of patient advocacy, a primary nursing responsibility. Little is known about whether research nurses experience unique ethical challenges distinct from those experienced by nurses in traditional patient-care settings. RESEARCH OBJECTIVES:: The purpose of the study was to describe the nature of ethical challenges experienced by clinical research nurses within the context of their practice. RESEARCH DESIGN:: The study utilized a qualitative descriptive design with individual interviews. PARTICIPANTS AND RESEARCH CONTEXT:: Participating nurses (N = 12) self-identified as having experienced ethical challenges during screening. The majority were Caucasian (90%), female (83%), and worked in outpatient settings (67%). Approximately 50% had > 10 years of research experience. ETHICAL CONSIDERATIONS:: The human subjects review board approved the study. Written informed consent was obtained. FINDINGS:: Predominant themes were revealed: (1) the inability to provide a probable good, or/do no harm, and (2) dual obligations (identity as a nurse vs a research nurse). The following patterns and subthemes emerged: conflicted allegiances between protocol implementation, needs of the participant, desire to advance science, and tension between the nurse-patient therapeutic relationship versus the research relationship. DISCUSSION:: Participants described ethical challenges specific to the research role. The issues are central to the nurse-participant relationship, patient advocacy, the nurse's role in implementing protocols, and/or advancing science. CONCLUSION:: Ethical challenges related to the specialized role of clinical research nurses were identified. More research is warranted to fully understand their nature and frequency and to identify support systems for resolution.

Development of a plain-language library of educational resources for research participants.

There is a paucity of educational resources for potential clinical trial participants, particularly resources in plain language, attentive to health literacy principles and translated into native languages. The New England Research Subject Advocacy Group was formed to explore common issues, interests, and concerns related to the experience of participation in clinical research and research participant safety. Specifically, the group sought to increase community awareness and trust through the development and distribution of publicly accessible informational resources. In support of these aims, the group developed a robust library of high-quality, plain-language educational materials covering topics in health research, research participation, and common research procedures, and translated the majority of the materials into an additional 15 languages. These resources have been downloaded over 130,000 times. After English, the most common languages downloaded are Vietnamese, Spanish, and Korean.

Cortisol inhibits CSF2 and CSF3 via DNA methylation and inhibits invasion in first-trimester trophoblast cells.

PROBLEM: Heightened maternal stress affects trophoblast function and increases risk for adverse pregnancy outcomes. METHODS OF STUDY: Studies were performed using the first-trimester trophoblast cell line, Sw.71. Cytokines were quantified using qPCR and ELISA. Epigenetic regulation of cytokines was characterized by inhibiting histone deacetylation (1 µmol/L suberoylanilide hydroxamic acid [SAHA]) or methylation (5 µmol/L 5-azacytidine), or with chromatin immunoprecipitation (ChIP) with a pan-acetyl histone-3 antibody. Invasion assays used Matrigel chambers. RESULTS: Cortisol inhibited expression of CSF2 (GM-CSF) and CSF3 (G-CSF) in trophoblast cells. Cortisol-associated inhibition was dependent on DNA methylation and was not affected by acetylation. There was also a modest decrease in trophoblast invasion, not dependent on loss of CSFs. CONCLUSION: In first-trimester trophoblast cells, the physiological glucocorticoid, cortisol, inhibited two cytokines with roles in placental development and decreased trophoblast invasion. Cortisol-associated changes in trophoblast function could increase the risk for immune-mediated abortion or other adverse pregnancy outcomes.

The Harvard Catalyst Common Reciprocal IRB Reliance Agreement: an innovative approach to multisite IRB review and oversight.

Reduction of duplicative Institutional Review Board (IRB) review for multiinstitutional studies is a desirable goal to improve IRB efficiency while enhancing human subject protections. Here we describe the Harvard Catalyst Master Reciprocal Common IRB Reliance Agreement (MRA), a system that provides a legal framework for IRB reliance, with the potential to streamline IRB review processes and reduce administrative burden and barriers to collaborative, multiinstitutional research. The MRA respects the legal autonomy of the signatory institutions while offering a pathway to eliminate duplicative IRB review when appropriate. The Harvard Catalyst MRA provides a robust and flexible model for reciprocal reliance that is both adaptable and scalable.

A distributed model: redefining a robust research subject advocacy program at the Harvard Clinical and Translational Science Center.

The Harvard Clinical and Translational Science Center ("Harvard Catalyst") Research Subject Advocacy (RSA) Program has reengineered subject advocacy, distributing the delivery of advocacy functions through a multi-institutional, central platform rather than vesting these roles and responsibilities in a single individual functioning as a subject advocate. The program is process-oriented and output-driven, drawing on the strengths of participating institutions to engage local stakeholders both in the protection of research subjects and in advocacy for subjects' rights. The program engages stakeholder communities in the collaborative development and distributed delivery of accessible and applicable educational programming and resources. The Harvard Catalyst RSA Program identifies, develops, and supports the sharing and distribution of expertise, education, and resources for the benefit of all institutions, with a particular focus on the frontline: research subjects, researchers, research coordinators, and research nurses.