Rhonda G. Kost

The challenges of collaboration for academic and community partners in a research partnership: Points to consider

The philosophical underpinning of Community-Engaged Research (CEnR) entails a collaborative partnership between academic researchers and the community. The Community-Based Participatory Research (CBPR) model is the partnership model most widely discussed in the CEnR literature and is the primary model we draw upon in this discussion of the collaboration between academic researchers and the community. In CPBR, the goal is for community partners to have equal authority and responsibility with the academic research team, and that the partners engage in respectful negotiation both before the research begins and throughout the research process to ensure that the concerns, interests, and needs of each party are addressed. The negotiation of a fair, successful, and enduring partnership requires transparency and understanding of the different assets, skills and expertise that each party brings to the project. Delineating the expectations of both parties and documenting the terms of agreement in a memorandum of understanding or similar document may be very useful. This document is structured to provide a “points- to-consider” roadmap for academic and community research partners to establish and maintain a research partnership at each stage of the research process.

Human Subjects Protections in Community-Engaged Research: A Research Ethics Framework

In the 30 years since the belmont Report, the role of the community in research has evolved and has taken on greater moral significance. Today, more and more translational research is being performed with the active engagement of individuals and communities rather than merely upon them. This engagement requires a critical examination of the range of risks that may arise when communities become partners in research. In attempting to provide such an examination, one must distinguish between established communities (groups that have their own organizational structure and leadership and exist regardless of the research) and unstructured groups (groups that may exist because of a shared trait but do not have defined leadership or internal cohesiveness). In order to participate in research as a community, unstructured groups must develop structure either by external means (by partnering with a Community-Based Organization) or by internal means (by empowering the group to organize and establish structure and leadership). When groups participate in research, one must consider risks to well-being due to process and outcomes. These risks may occur to the individual qua individual, but there are also risks that occur to the individual qua member of a group and also risks that occur to the group qua group. There are also risks to agency, both to the individual and the group. A 3-by-3 grid including 3 categories of risks (risks to well-being secondary to process, risks to well-being secondary to outcome and risks to agency) must be evaluated against the 3 distinct agents: Individuals as individual participants, individuals as members of a group (both as participants and as nonparticipants) and to communities as a whole. This new framework for exploring the risks in community-engaged research can help academic researchers and community partners ensure the mutual respect that community-engaged research requires.

Research Ethics Education for Community-Engaged Research: A Review and Research Agenda

Community engagement is increasingly becoming an integral part of research. “Community-engaged research” (CEnR) introduces new stakeholders as well as unique challenges to the protection of participants and the integrity of the research process. We—a group of representatives of CTSA-funded institutions and others who share expertise in research ethics and CEnR—have identified gaps in the literature regarding (1) ethical issues unique to CEnR; (2) the particular instructional needs of academic investigators, community research partners, and IRB members; and (3) best practices for teaching research ethics. This paper presents what we know, as well as what we still need to learn, in order to develop quality research ethics educational materials tailored to the full range of stakeholder groups in CEnR.

virologic and Immunologic Effect of Antiretroviral Therapy on Hiv-1 in Gut-associated Lymphoid Tissue

Objectives: We evaluated virologic and immunologic responses to antiretroviral therapy in gut‐associated lymphoid tissue (GALT) compared with those found in peripheral blood. Methods: Eight HIV‐1‐infected individuals were treated with three reverse transcriptase inhibitors and one protease inhibitor. Endoscopic biopsies were performed at baseline, and at months 1, 2, and 6. We measured the level of cell‐associated multiply spliced and unspliced HIV‐1 mRNA in GALT and in peripheral blood mononuclear cells. Immunologic responses were assessed by flow cytometry. Results: Levels of multiply spliced HIV‐1 mRNA declined in parallel fashion both in peripheral blood and GALT. After 6 months of therapy, unspliced HIV‐1 mRNA in the GALT was below assay detection although it persisted in peripheral blood mononuclear cells in 4 study subjects. Although the percentage of CD4+ lymphocytes increased significantly in peripheral blood, only modest increases occurred in GALT. The percentage of activated CD8+ T cells decreased significantly in peripheral blood whereas only modest reductions occurred in GALT. Conclusions: Antiretroviral therapy effectively suppressed HIV‐1 replication in GALT. The percentage of CD4+ T cells in peripheral blood uniformly increased in all study subjects, whereas it was more variable in the GALT.

Assessing Research Participants’ Perceptions of their Clinical Research Experiences

Introduction: Participants’ perceptions of their research experiences provide valuable measures of ethical treatment, yet no validated instruments exist to measure these experiences. We conducted focus groups of research participants and professionals as the initial step in developing a validated instrument.

Nine key functions for a human subjects protection program for community-engaged research: points to consider.

The ethical conduct of community-engaged research (CEnR), of which the Community-Based Participatory Research (CBPR) model is the partnership model most widely discussed in the CEnR literature and is the primary model we draw upon in this discussion, requires an integrated and comprehensive human subjects protection (HSP) program that addresses the additional concerns salient to CEnR where members of a community are both research partners and participants. As delineated in the federal regulations, the backbone of a HSP program is the fulfillment of nine functions: (1) minimize risks; (2) reasonable benefit-risk ratio; (3) fair subject selection; (4) adequate monitoring; (5) informed consent; (6) privacy and confidentiality; (7) conflicts of interest; (8) address vulnerabilities; and (9) HSP training. The federal regulations, however, do not consider the risks and harms that may occur to groups, and these risks have not traditionally been included in the benefit: Risk analysis nor have they been incorporated into an HSP framework. We explore additional HSP issues raised by CEnR within these nine ethical functions. Various entities exist that can provide HSP—the investigator, the Institutional Review Board, the Conflict of Interest Committee, the Research Ethics Consultation program, the Research Subject Advocacy program, the Data and Safety Monitoring Plan, and the Community Advisory Board. Protection is best achieved if these entities are coordinated to ensure that no gaps exist, to minimize unnecessary redundancy, and to provide checks and balances between the different entities of HSP and the nine functions that they must realize. The document is structured to provide a “points-to-consider” roadmap for HSP entities to help them adequately address the nine key functions necessary to provide adequate protection of individuals and communities in CEnR.

Molecular Types of Methicillin-Resistant Staphylococcus aureus and Methicillin-Sensitive S. aureus Strains Causing Skin and Soft Tissue Infections and Nasal Colonization, Identified in Community Health Centers in New York City

ABSTRACT In November 2011, The Rockefeller University Center for Clinical and Translational Science (CCTS), the Laboratory of Microbiology and Infectious Diseases, and Clinical Directors Network (CDN) launched a research and learning collaborative project with six community health centers in the New York City metropolitan area to determine the nature (clonal type) of community-acquired Staphylococcus aureus strains causing skin and soft tissue infections (SSTIs). Between November 2011 and March 2013, wound and nasal samples from 129 patients with active SSTIs suspicious for S. aureus were collected and characterized by molecular typing techniques. In 63 of 129 patients, the skin wounds were infected by S. aureus: methicillin-resistant S. aureus (MRSA) was recovered from 39 wounds and methicillin-sensitive S. aureus (MSSA) was recovered from 24. Most—46 of the 63–wound isolates belonged to the CC8/Panton-Valentine leukocidin-positive (PVL+) group of S. aureus clone USA300: 34 of these strains were MRSA and 12 were MSSA. Of the 63 patients with S. aureus infections, 30 were also colonized by S. aureus in the nares: 16 of the colonizing isolates were MRSA, and 14 were MSSA, and the majority of the colonizing isolates belonged to the USA300 clonal group. In most cases (70%), the colonizing isolate belonged to the same clonal type as the strain involved with the infection. In three of the patients, the identity of invasive and colonizing MRSA isolates was further documented by whole-genome sequencing.

Open-label phase II trial of amprenavir, abacavir, and fixed-dose zidovudine/lamivudine in newly and chronically HIV-1--infected patients.

Summary: A Phase II clinical trial was designed to evaluate the efficacy and tolerability of twice‐daily abacavir, amprenavir, and zidovudine (ZDV)/lamivudine (3TC) in HIV‐1‐infected study subjects naive to protease inhibitors and 3TC. Plasma and cerebrospinal fluid (CSF) HIV‐1 RNA levels and T‐cell subsets were measured. In all, 27 newly diagnosed and 12 chronically HIV‐1‐infected study subjects are included in the analysis. Week 48 plasma HIV‐1 RNA levels were <500 copies/ml in 100% of study subjects, and <50 copies/ml in 80% of chronically infected and 100% of newly infected study subjects. The mean change in CD4 was +150 cells/&mgr;l (newly infected, p < .001), and +155 cells/&mgr;l (chronically infected, p < .001). At Week 48, evidence of cellular activation persisted in both cohorts. A twice‐daily regimen of amprenavir, abacavir, and ZDV/3TC affords potent viral suppression and significant increases in total CD4+ cells in HIV‐1‐infected study subjects. Patient intolerance may limit the efficacy of this combination.

Development of a Research Participants’ Perception Survey to Improve Clinical Research

Introduction: Clinical research participants’ perceptions regarding their experiences during research protocols provide outcome‐based insights into the effectiveness of efforts to protect rights and safety, and opportunities to enhance participants’ clinical research experiences. Use of validated surveys measuring patient‐centered outcomes is standard in hospitals, yet no instruments exist to assess outcomes of clinical research processes.

Accrual and recruitment practices at Clinical and Translational Science Award (CTSA) Institutions: A call for expectations, expertise, and evaluation

Purpose To respond to increased public and programmatic demand to address underenrollment of clinical translational research studies, the authors examined participant recruitment practices at Clinical and Translational Science Award (CTSA) sites and make recommendations for performance metrics and accountability. Method The CTSA Recruitment and Retention taskforce in 2010 invited representatives at 46 CTSAs to complete an online 48-question survey querying accrual and recruitment outcomes, practices, evaluation methods, policies, and perceived gaps in related knowledge/practice. Descriptive statistical and thematic analyses were conducted. Results Forty-six respondents representing 44 CTSAs completed the survey. Recruitment conducted by study teams was the most common practice reported (78%–91%, by study type); 39% reported their institution offered recruitment services to investigators. Respondents valued study feasibility assessment as a successful practice (39%); desired additional resources included feasibility assessments (49%) and participant registries (44%). None reported their institution systematically required justification of feasibility; some indicated relevant information was considered prior to institutional review board (IRB) review (30%) or contract approval (22%). All respondents’ IRBs tracked study progress, but only 10% of respondents could report outcome data for timely accrual. Few reported written policies addressing poor accrual or provided data to support recruitment practice effectiveness. Conclusions Many CTSAs lack the necessary frame work to support study accrual. Recom men dations to enhance accrual include articulating institutional expectations and policy for routine recruitment plan ning; providing recruitment expertise to inform feasibility assessment and recruit ment planning; and developing interdepartmental coordination and integrated informatics infrastructure to drive the conduct, evaluation, and improvement of recruitment practices.