Experts In Clinical Research Research Articles

104 Perceived Barriers to the Recruitment and Retention of Underrepresented Racial and Ethnic Groups (URGs) in Clinical Research

OBJECTIVES/GOALS: The inclusion of underrepresented racial and ethnic groups (URGs) in clinical research is critical for ethical and scientific reasons. This initiative aimed to assess the perspectives, barriers, needs, and recommendations encountered by research teams when enrolling and retaining URGs in clinical research. METHODS/STUDY POPULATION: An anonymous, web-based survey comprised of quantitative and qualitative questions was administered to individuals involved in clinical research at an academic medical center. The survey assessed three main domains: 1. Research teams' perceptions and experiences with enrolling URGs in clinical research, 2. Factors that discourage URGs from participating in clinical research, and 3. Research teams’ overall willingness to support URG enrollment. Demographics were also collected. The survey was reviewed by experts in clinical research, research ethics, and diversity, equity, inclusion, and accessibility (DEIA). The assessment was piloted among research professionals and edits were made accordingly prior to official dissemination. Data were analyzed using descriptive statistics. RESULTS/ANTICIPATED RESULTS: There was a total of 63 responses. A majority of respondents have more success enrolling patients whose primary language is the same as their own and that time arranging for an interpreter has negatively impacted enrollment efforts. Approximately half of the respondents believe that the race and/or ethnicity of the potential study participant influences enrollment success. Factors discouraging URGs from participating in clinical research include unavailability for follow-up visits due to transportation issues, distrust in doctors and/or researchers, fear of unknown side effects, and unavailability of medical interpreters. Respondents report that they are not discouraged from enrolling URGs and would utilize resources related to encouraging the inclusion of URGs DISCUSSION/SIGNIFICANCE: Language appears more influential than ethnicity or race when it comes to enrolling and retaining URGs. Additionally, it appears that enrolling is a bigger challenge than retaining. Major themes that emerge with respect to retaining enrolled participants include the inability to attend follow-up visits and the lack of incentives/compensation.

Strengthening research networks: Insights from a clinical research network in Brazil.

Clinical Research Networks (CRNs) are means to improve healthcare delivery, quality of care and patient outcomes. The Oswaldo Cruz Foundation (Fiocruz), Latin America's leading health research organization, has established a CRN to promote interaction and collaboration among its clinical research experts. After a decade of operation, a revitalization process was undertaken out of the need to improve its functionality. This study aimed to describe the evaluation process of the Fiocruz Clinical Research Network (RFPC) by gathering the opinions and perspectives of its members and identifying the network structure. The goal was to improve scientific collaboration and member engagement, thereby increasing the integration, effectiveness, and impact of clinical research conducted at the institution. Clinical research professionals at Fiocruz were invited to participate in an online questionnaire to collect information about their professional experience, the benefits and constraints of participating in research networks, relevant discussion topics, and the challenges of complying with Good Clinical Practices (GCP). With the help of social network analysis, a deeper understanding of the dynamics and structure of professional communication networks was obtained. The questionnaire was completed by 122 professionals (response rate 50.4%), with most respondents being principal investigators (PIs) with more than 10 years of professional experience (24.6%). Participation in research networks was considered beneficial, particularly in working groups (48.4%), and as an opportunity to exchange experiences with other professionals (44.3%). Almost half of the participants (48.4%) did not identify any barriers to participating in a network. Topics that required further discussion included data management, biorepositories and biobanks, and ethical and regulatory issues. Challenges to conducting clinical research with GCP standards included strategic support and funding, staffing and training, data management, infrastructure, quality management, and collaboration. Communication within the research network was loosely structured, with the most experienced professionals holding central positions. This analysis provided valuable insights to support the management of the RFPC. It highlighted the internal community's interests and expectations, identified key areas for improvement in GCP implementation, and influential professionals who could improve information sharing and national integration. The findings have far-reaching implications that can be applied in different contexts. They contribute to the ongoing discussion on the establishment and management of research networks.

Primary Care Family Physicians’ Experiences with Clinical Integration: A Scoping Review of Qualitative and Mixed Reviews

Background: Clinical (service) integration in primary care settings describes how healthcare services are coordinated over time across healthcare contexts to meet patient care needs. Promoting integrated care with interventions that lack systematic approaches can unintentionally increase the complexity and fragmentation of the healthcare system. To improve care integration and healthcare service planning, a systematic approach to understanding its many influencing factors is paramount. This phase I study aims to generate a comprehensive map of family physician (FP) perceived factors, across diseases and patient demographics, influencing how services are integrated for patients. 
 Methods: The protocol development is guided by Arksey and O’Malley’s scoping review methodology framework. Keywords and MeSH terms were contributed by a multidisciplinary team of healthcare professionals, researchers, and patient representatives through an iterative discussion. An Information Specialist with clinical research expertise tested keywords and MeSH terms to build a search strategy using MEDLINE. The strategy was then adjusted for the EMBASE and CINAHL databases. All identified articles were imported into Covidence platform, and 228 duplicates were removed. Two independent reviewers screened 1,771 studies by their titles and abstracts. Of them, 264 studies were reviewed in full text against the selection criteria and their references were hand-searched. A total of 91 articles were included, and over 2,800 factors were extracted. The factors are being or will be coded into themes the Clinical Integration Framework, a merging of two existing models identified from literature and modified. Within each theme, similar codes are clustered together as a subtheme. 
 Discussion: The identified factors will help develop a survey in Phase II study to ascertain high impact factors for intervention(s), as well as thematic and evidence gaps to guide future research. The study findings will be shared with stakeholders to promote awareness of clinical integration issues through multiple channels: publications and conferences for researchers and care providers, an executive summary for clinical leaders and policy makers, and social media for the public.

The development of the Belgian paediatric clinical trial network

ABSTRACT Paediatric clinical trials are critical to ensure that medications prescribed to children are safe and effective. However, evidence-based dosing and labelling of such medications remain limited, and most clinical trials in paediatrics fail. Factors for lack of trial completion include performance at site level (limited patient recruitment, limited site staff experience and lack of infrastructure), the sponsor team (limited paediatric specific expertise in design, uncertainties on robustness of biomarkers or outcome variables) as well as regulatory and administrative burdens. As a result of the growing demand for site support, the Belgian Paediatric Clinical Research Network (BPCRN) established in 2009 has been relaunched in 2018 to improve paediatric clinical trials, with the support of innovative-medicines-initiative 2 (IMI2) pan-European network conect4children (c4c) and the transatlantic network I-ACT for Children (US). This paper highlights the formation of the BPCRN and the practical insights it offers for advancing paediatric clinical trials through national networks. A national network can improve trial quality, safety and efficiency, provide clinical research expertise, identify suitable sites, and help with troubleshooting of common trial issues. The BPCRN’s centralized approach has advanced paediatric clinical trials by streamlining communication and standardizing trial conduct. Challenges and opportunities have arisen, including a relaunch in 2018, orphan medicine trials, and network sustainability. Collaboration between network activities, government support, site-level improvements, efficient communication, and interaction with industry are key to achieve lasting transformation in paediatric medicine research.

Assessing Obesogenic School Environments in Sibiu County, Romania: Adapting the ISCOLE School Environment Questionnaire.

The impact of the school environment on childhood weight status has garnered significant attention in recent years. This study aimed to adapt and validate the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) School and Environment questionnaire in order to assess the potential obesogenic impact of school environments in Sibiu County, Romania. The ISCOLE questionnaire was chosen for its rigorous methodology. It was derived from a comprehensive study conducted across 12 countries which aimed to capture multifaceted influences on childhood weight while emphasizing educational settings in the collection of data. To guide the translation and adaptation of the questionnaire, a multidisciplinary committee was assembled which comprised experts in teaching and school administration to ensure target responder relevance, experts in clinical research to ensure methodological robustness, experts in language adaptation to preserve the original intent of the survey, and experts in public health to steer the interpretation of the results, with potential policy implications. The data were analyzed by distinguishing between urban and rural settings, and a two-step cluster analysis was implemented to identify potential intervention targets. To assess the validity of the adapted tool, the questionnaire's construct validity and internal consistency were explored. A response rate of 71.2% of the approached schools in Sibiu County was achieved. Of the 84 responding school representatives, 37 (44%) were from a rural setting. The rural schools had significantly more limited access to gymnasiums, secured lockers, showers, and bicycle racks, and exhibited more serious problems regarding the inadequate disposal of garbage in the school vicinity. A two-step cluster analysis revealed distinct school categories, providing opportunities for public policy interventions. One of these primarily concerned rural schools with limited infrastructure but with proactive practices and policies which were termed "unable but willing"; on the opposing spectrum, the category "able but unwilling" mainly comprised urban schools which had available facilities but lacked local proactive initiatives. The findings emphasize the urgent need for targeted measures to bridge these discrepancies by investing in infrastructure in rural schools and promoting active school practices and policies in urban settings. The assessment of obesogenic school environments in Sibiu County provides a pilot model for broader applications due to the diverse school landscape and supportive local authorities. The results, which were achieved using low-cost methods, can guide future educational policies, health promotion initiatives, and preventive interventions.

Key Contributions by the Swiss Tropical and Public Health Institute Towards New and Better Drugs for Tropical Diseases.

Thanks to its expertise in clinical research, epidemiology, infectious diseases, microbiology, parasitology, public health, translational research and tropical medicine, coupled with deeply rooted partnerships with institutions in low- and middle-income countries (LMICs), the Swiss Tropical and Public Health Institute (Swiss TPH) has been a key contributor in many drug research and development consortia involving academia, pharma and product development partnerships. Our know-how of the maintenance of parasites and their life-cycles in the laboratory, plus our strong ties to research centres and disease control programme managers in LMICs with access to field sites and laboratories, have enabled systems for drug efficacy testing in vitro and in vivo, clinical research, and modelling to support the experimental approaches. Thus, Swiss TPH has made fundamental contributions towards the development of new drugs - and the better use of old drugs - for neglected tropical diseases and infectious diseases of poverty, such as Buruli ulcer, Chagas disease, food-borne trematodiasis (e.g. clonorchiasis, fascioliasis and opisthorchiasis), human African trypanosomiasis, leishmaniasis, malaria, schistosomiasis, soil-transmitted helminthiasis and tuberculosis. In this article, we show case the success stories of molecules to which Swiss TPH has made a substantial contribution regarding their use as anti-infective compounds with the ultimate aim to improve people's health and well-being.

Methotrexate for inflammatory skin disease in pediatric patients: Consensus treatment guidelines.

Methotrexate (MTX) is a readily accessible drug, first used in 1948 and employed for a wide variety of indications since then. However, despite widespread off-label use, FDA labeling does not include approved indications for the use of MTX for many inflammatory skin diseases in pediatric patients, including morphea, psoriasis, atopic dermatitis, and alopecia areata, among others. Without published treatment guidelines, some clinicians may be hesitant to use MTX off-label, or uncomfortable prescribing MTX in this population. To address this unmet need, an expert consensus committee was convened to develop evidence- and consensus-based guidelines for use of MTX to treat pediatric inflammatory skin disease. Clinicians with experience and expertise in clinical research, drug development, and treating inflammatory skin disease in pediatric patients with MTX were recruited. Five committees were created based on major topic areas: (1) indications and contraindications, (2) dosing, (3) interactions with immunizations and medications, (4) adverse effects (potential for and management of), and (5) monitoring needs. Pertinent questions were generated and addressed by the relevant committee. The entire group participated in a modified Delphi process to establish agreement on recommendations for each question. The committee developed 46 evidence- and consensus-based recommendations, each with >70% agreement among members, across all five topics. These are presented in tables and text, along with a discussion of supporting literature, and level of evidence. These evidence- and consensus-based recommendations will support safe and effective use of MTX for the underserved population of pediatric patients who may benefit from this valuable, time-honored medication.

Using the Delphi process to determine the minimum clinically important effect size for the Balanced-2 randomised controlled trial.

The sample size calculation is an important step in designing randomised controlled trials. For a trial comparing a control and an intervention group, where the outcome is binary, the sample size calculation requires choosing values for the anticipated event rates in both the control and intervention groups (the effect size), and the error rates. The Difference ELicitation in TriAls guidance recommends that the effect size should be both realistic, and clinically important to stakeholder groups. Overestimating the effect size leads to sample sizes that are too small to reliably detect the true population effect size, which in turn results in low achieved power. In this study, we use the Delphi approach to gain consensus on what the minimum clinically important effect size is for Balanced-2, a randomised controlled trial comparing processed electroencephalogram-guided 'light' to 'deep' general anaesthesia on the incidence of postoperative delirium in older adults undergoing major surgery. Delphi rounds were conducted using electronic surveys. Surveys were administered to two stakeholder groups: specialist anaesthetists from a general adult department in Auckland City Hospital, New Zealand (Group 1), and specialist anaesthetists with expertise in clinical research, identified from the Australian and New Zealand College of Anaesthetist's Clinical Trials Network (Group 2). A total of 187 anaesthetists were invited to participate (81 from Group 1 and 106 from Group 2). Results from each Delphi round were summarised and presented in subsequent rounds until consensus was reached (>70% agreement). The overall response rate for the first Delphi survey was 47% (88/187). The median minimum clinically important effect size was 5.0% (interquartile range: 5.0-10.0) for both stakeholder groups. The overall response rate for the second Delphi survey was 51% (95/187). Consensus was reached after the second round, as 74% of respondents in Group 1 and 82% of respondents in Group 2 agreed with the median effect size. The combined minimum clinically important effect size across both groups was 5.0% (interquartile range: 3.0-6.5). This study demonstrates that surveying stakeholder groups using a Delphi process is a simple way of defining a minimum clinically important effect size, which aids the sample size calculation and determines whether a randomised study is feasible.

Automated generation of comparator patients in the electronic medical record.

Well-designed randomized trials provide high-quality clinical evidence but are not always feasible or ethical. In their absence, the electronic medical record (EMR) presents a platform to conduct comparative effectiveness research, central to the emerging academic learning health system (aLHS) model. A barrier to realizing this vision is the lack of a process to efficiently generate a reference comparison group for each patient. To test a multi-step process for the selection of comparators in the EMR. We conducted a mixed-methods study within a large aLHS in North Carolina. We (1) created a list of 35 candidate variables; (2) surveyed 270 researchers to assess the importance of candidate variables; and (3) built consensus rankings around survey-identified variables (ie, importance scores >7) across two panels of 7-8 clinical research experts. Prioritized algorithm inputs were collected from the EMR and applied using a greedy matching technique. Feasibility was measured as the percentage of patients with 100 matched comparators and performance was measured via computational time and Euclidean distance. Nine variables were selected: age, sex, race, ethnicity, body mass index, insurance status, smoking status, Charlson Comorbidity Index, and neighborhood percentage in poverty. The final process successfully generated 100 matched comparators for each of 1.8 million candidate patients, executed in less than 100 min for the majority of strata, and had average Euclidean distance 0.043. EMR-derived matching is feasible to implement across a diverse patient population and can provide a reproducible, efficient source of comparator data for observational studies, with additional testing in clinical research applications needed.

Proposal of a Case Reporting Draft Guideline for Pharmacopuncture: Literature Review of Pharmacopuncture Case Reports

Pharmacopuncture is a popular treatment that combines the advantages of both herbal medicine and acupuncture. However, pharmacopuncture care reporting guidelines have not yet been developed. This study aimed to propose a reporting guideline draft for pharmacopuncture case reports. Pharmacopuncture case reports were retrieved from 4 databases (KCI, RISS, ScienceON, OASIS) to analyze the items reported and their fidelity. We analyzed 5 existing reporting guidelines related to Korean medicine case reporting to identify the items to be included in the extension of pharmacopuncture reporting guidelines. From 3,684 studies, 29 case reports were included and 4 items were identified as not reported in enough detail: “direction and depth of pharmacopuncture” (89.5%); “method of manufacturing the syringe needle” (82.8%); “posture of the patient during the therapy” (75.9%); and “pharmacopuncture recipe” (69.5%). As a result of analyzing moxibustion and acupuncture clinical trial reporting guidelines, it was determined that detailed reporting guidelines on the type of pharmacopuncture, manufacturing method, and treatment method were required and we propose that a pharmacopuncture reporting guideline draft should include these details. Further investigations are warranted using the Delphi technique to reach agreement with clinical practitioners and clinical research experts.

The Roles of a Secondary Data Analytics Tool and Experience in Scientific Hypothesis Generation in Clinical Research: Protocol for a Mixed Methods Study.

BackgroundScientific hypothesis generation is a critical step in scientific research that determines the direction and impact of any investigation. Despite its vital role, we have limited knowledge of the process itself, thus hindering our ability to address some critical questions.ObjectiveThis study aims to answer the following questions: To what extent can secondary data analytics tools facilitate the generation of scientific hypotheses during clinical research? Are the processes similar in developing clinical diagnoses during clinical practice and developing scientific hypotheses for clinical research projects? Furthermore, this study explores the process of scientific hypothesis generation in the context of clinical research. It was designed to compare the role of VIADS, a visual interactive analysis tool for filtering and summarizing large data sets coded with hierarchical terminologies, and the experience levels of study participants during the scientific hypothesis generation process.MethodsThis manuscript introduces a study design. Experienced and inexperienced clinical researchers are being recruited since July 2021 to take part in this 2×2 factorial study, in which all participants use the same data sets during scientific hypothesis–generation sessions and follow predetermined scripts. The clinical researchers are separated into experienced or inexperienced groups based on predetermined criteria and are then randomly assigned into groups that use and do not use VIADS via block randomization. The study sessions, screen activities, and audio recordings of participants are captured. Participants use the think-aloud protocol during the study sessions. After each study session, every participant is given a follow-up survey, with participants using VIADS completing an additional modified System Usability Scale survey. A panel of clinical research experts will assess the scientific hypotheses generated by participants based on predeveloped metrics. All data will be anonymized, transcribed, aggregated, and analyzed.ResultsData collection for this study began in July 2021. Recruitment uses a brief online survey. The preliminary results showed that study participants can generate a few to over a dozen scientific hypotheses during a 2-hour study session, regardless of whether they used VIADS or other analytics tools. A metric to more accurately, comprehensively, and consistently assess scientific hypotheses within a clinical research context has been developed.ConclusionsThe scientific hypothesis–generation process is an advanced cognitive activity and a complex process. Our results so far show that clinical researchers can quickly generate initial scientific hypotheses based on data sets and prior experience. However, refining these scientific hypotheses is a much more time-consuming activity. To uncover the fundamental mechanisms underlying the generation of scientific hypotheses, we need breakthroughs that can capture thinking processes more precisely.International Registered Report Identifier (IRRID)DERR1-10.2196/39414

Consensus Recommendations on the Treatment of Opioid Use Disorder in the Emergency Department

The treatment of opioid use disorder with buprenorphine and methadone reduces morbidity and mortality in patients with opioid use disorder. The initiation of buprenorphine in the emergency department (ED) has been associated with increased rates of outpatient treatment linkage and decreased drug use when compared to patients randomized to receive standard ED referral. As such, the ED has been increasingly recognized as a venue for the identification and initiation of treatment for opioid use disorder, but no formal American College of Emergency Physicians (ACEP) recommendations on the topic have previously been published. The ACEP convened a group of emergency physicians with expertise in clinical research, addiction, toxicology, and administration to review literature and develop consensus recommendations on the treatment of opioid use disorder in the ED. Based on literature review, clinical experience, and expert consensus, the group recommends that emergency physicians offer to initiate opioid use disorder treatment with buprenorphine in appropriate patients and provide direct linkage to ongoing treatment for patients with untreated opioid use disorder. These consensus recommendations include strategies for opioid use disorder treatment initiation and ED program implementation. They were approved by the ACEP board of directors in January2021.

Exploring new uses for existing drugs: innovative mechanisms to fund independent clinical research

BackgroundFinding new therapeutic uses for existing medicines could lead to safe, affordable and timely new treatment options for patients with high medical needs. However, due to a lack of economic incentives, pharmaceutical developers are rarely interested to invest in research with approved medicines, especially when they are out of basic patent or regulatory protection. Consequently, potential new uses for these medicines are mainly studied in independent clinical trials initiated and led by researchers from academia, research institutes, or collaborative groups. Yet, additional financial support is needed to conduct expensive phase III clinical trials to confirm the results from exploratory research.MethodsIn this study, scientific and grey literature was searched to identify and evaluate new mechanisms for funding clinical trials with repurposed medicines. Semi-structured interviews were conducted with 16 European stakeholders with expertise in clinical research, funding mechanisms and/or drug repurposing between November 2018 and February 2019 to consider the future perspectives of applying new funding mechanisms.ResultsTraditional grant funding awarded by government and philanthropic organisations or companies is well known and widely implemented in all research fields. In contrast, only little research has focused on the application potential of newer mechanisms to fund independent clinical research, such as social impact bonds, crowdfunding or public-private partnerships. Interviewees stated that there is a substantial need for additional financial support in health research, especially in areas where there is limited commercial interest. However, the implementation of new funding mechanisms is facing several practical and financial challenges, such as a lack of expertise and guidelines, high transaction costs and difficulties to measure health outcomes. Furthermore, interviewees highlighted the need for increased collaboration and centralisation at a European and international level to make clinical research more efficient and reduce the need for additional funding.ConclusionsNew funding mechanisms to support clinical research may become more important in the future but the unresolved issues identified in the current study warrant further exploration.

Recommendations for enhancing collaboration between the Canadian emergency department quality improvement and research communities.

ObjectivesWhile quality improvement (QI) and clinical research embody two distinct scientific approaches, they have the same ultimate goal—to improve health and patient care outcomes. By leveraging their respective strengths there is a higher likelihood of achieving and sustaining health improvements. Our objective was to create recommendations to enhance the collaboration of the Canadian emergency medicine QI and clinical research communities.MethodsAn expert panel of eight ED clinicians with diverse QI and clinical research expertise drafted a list of recommendations based on their professional expertise and a scoping review of the literature. These recommendations were refined through consultation with national stakeholders and reviewed at the 2020 CAEP Virtual Academic Symposium, where feedback was received through several virtual platforms.ResultsThe final six recommendations include that all emergency medicine providers should: (1) understand the role and application of both clinical research and QI science; that academic emergency medicine physicians should: (2) contribute to both local adoption and broad dissemination of project findings, (3) leverage QI methodologies in research projects to improve knowledge translation, and (4) ensure that project outcomes prioritize patient care; and that academic leaders should: (5) enhance the infrastructure for oversight of research and QI projects, and (6) encourage collaboration between researchers and QI experts by ensuring that academic and operational infrastructures align and support both.ConclusionSix recommendations are presented to help the Canadian emergency medicine community achieve greater collaboration between researchers and QI experts with the ultimate goal of improving patient care outcomes.

Propagandizing anti-vaccination: Analysis of Vaccines Revealed documentary series

Politically charged health propaganda films may have public health ramifications through decreased vaccination uptake, especially with expansive dissemination potential on social media. The nine-episode documentary series Vaccines Revealed, touted as foremost truth within the largest anti-vaccination closed Facebook group, advocates for non-medical childhood vaccination exemptions — a policy actively opposed by the American Academy of Pediatrics. This series is recommended specifically to parents who are on the fence about whether or not to vaccinate their children as well as new, first-time, and expectant mothers.Fourteen 'expert' panelists included: six M.D,'s who reportedly prefer natural approaches for everything from chiropractic to cardiology practice, a vaccine injury attorney, two professors, one psychiatrist, the founder of natural search engine Greenmedinfo.com, a nationally-recognized clinical research expert on the HPV vaccine, the president of the National Vaccine Information Center, and three parents of vaccine-injured children. Additionally, voiceover clips from an epidemiologist and former senior scientist at the CDC were played throughout the series as evidence of governmental conspiracy. Inclusion of these testimonies, particularly from white coat doctors, led to a perception of high source credibility.Qualitative analysis of this documentary series revealed five overarching themes: (perceived) solidified science, collusion and conspiracy, canary in the coal mine, fear appeals, and the morality and necessity of individual choice.As opposed to formulating a priori theoretical assumptions, grounded theory allowed an integrative theoretical explanation to emerge from the data. Researchers expanded cognitive dissonance, parasocial interaction, and social identification theories and described how viewers of Vaccines Revealed could come to align their views on vaccinations with those of the panelists featured in the videos.

A hospital-based treatment of suicide attempt patients with problematic alcohol use: Rationale and treatment development

ObjectiveProblematic alcohol use (PAU) is a potent risk factor for suicidal behavior yet individuals with PAU presenting to hospital with suicidal risk may receive less intensive hospital-based treatment than suicidal patients without PAU. Developing efficacious interventions for at-risk patients with PAU that may be delivered in hospital is critical, particularly for those hospitalized following a suicide attempt, a group at marked risk. MethodThe authors identified the Attempted Suicide Short Intervention Program (ASSIP) for adaption for hospitalized suicide attempt patients with PAU because of its flexibility, brevity, and evidence of efficacy to reduce risk for suicide reattempt. After consulting with the developers of ASSIP, clinical research experts in the treatment of suicidal risk and PAU, and treatment providers of hospitalized suicide attempt patients, the authors made modifications to ASSIP to tailor it to hospitalized suicide attempt patients with PAU.Results and conclusionOur modifications to ASSIP include highlighting links between PAU and the timing of the attempt; integrating such links into the narrative story of the attempt, the written case formulation, and the homework task; and identifying concrete strategies to address PAU-related risk in the prevention plan. These modifications are the focus of an ongoing treatment development study.

Experimental model systems for preclinical research on Waldenström macroglobulinemia

Waldenstr?m macroglobulinemia (WM) is an incurable low-grade lymphoplasmacytic lymphoma of mature IgM⁺ B-lymphocytes that warrants additional research to increase therapeutic options, enhance quality of life, and improve survival of patients with WM. Here we concluded a miniseries of short reviews on the diagnosis and treatment ^[1], natural history ^[2] and putative cell-of-origin of WM ^[3] with a brief survey of preclinical experimental model systems available for fundamental and translational research studies on this enigmatic neoplasm. The model systems comprise of: ① continuous tumor cell lines, three of which are well authenticated and demonstrated to be derived from the patient's index tumor; ② human-in-mouse xenografts that rely on immunodeficient laboratory mice, adapted to carry small fragments of implanted human bone, to provide a suitable microenvironment for incoming lymphoma cells; and ③ genetically engineered mouse models (GEMMs) of neoplastic B-cell development, in which WM-like tumors arise spontaneously in the presence of fully functional innate and adaptive immune systems. Because none of the models developed thus far are perfect, additional efforts are required to achieve a better preclinical representation of disease characteristics of WM. To achieve that goal, the active involvement of basic and clinical research experts from China is called for, so novel drugs and immunotherapies for WM will reach clinics sooner, thereby ensuring the future of patients with WM will be brighter.

US Patient-Centered Research Priorities and Roadmap for Bronchiectasis

Noncystic fibrosis bronchiectasis (bronchiectasis) is an increasingly common chronic lung disease that is difficult to manage because of a lack of evidence on which to base treatment decision-making. We sought to develop a practical list of US-based patient-centered research priorities and an associated roadmap to guide bronchiectasis research. We designed and administered a web-based patient needs assessment survey to establish broad research priorities, convened three stakeholder webinars to confirm the top priorities, obtained written stakeholder feedback, and completed a final consensus survey of objectives. The stakeholder panel consisted of clinical research experts in bronchiectasis, a seven-member patient advisory panel, and representatives from the two key patient advocacy organizations: COPD Foundation and NTM Info and Research Inc. Based on survey results from 459 patients with bronchiectasis, the stakeholder panel identified 27 patient-centered research priorities for bronchiectasis in the areas of bronchiectasis treatment and prevention of exacerbations, improving treatment of exacerbations and infections, improving health-related quality of life, predictors of poor prognosis, understanding the impact of underlying conditions, and conducting patient-centered clinical trials. These priorities should further inform the development and evaluation of both new and previously unproven therapies, with particular attention to the inclusion of patient-reported outcomes. We anticipate a great deal of progress will be made in the field of bronchiectasis in the next decade.

Academic response to improving value and reducing waste: A comprehensive framework for INcreasing QUality In patient-oriented academic clinical REsearch (INQUIRE).

BackgroundCompelling evidence has demonstrated that a large proportion of investment in biomedical research is wasted; this waste is avoidable. Academic institutions have, thus far, shown limited response to recommendations for increasing value and reducing waste. We formulated an academic response by (i) achieving consensus across a wide range of stakeholder groups on a comprehensive framework for quality of patient-oriented clinical research and (ii) highlighting first successful examples of its operationalization to facilitate waste-reducing strategies at academic institutions.Methods and findingsBased on a systematic review of quality definitions, concepts, and criteria in the medical literature (systematic MEDLINE search up to February 15, 2015, with independent and in duplicate article selection) and on stakeholder websites from 13 countries (Australia, Austria, Canada, France, Germany, Italy, Japan, Norway, Spain, Sweden, Switzerland, United Kingdom, and United States), we systematically developed a comprehensive framework for the quality of clinical research. We identified websites through personal contacts with experts in clinical research or public health who also suggested, for each country, websites of the following 7 stakeholder groups: patient organizations; academic research infrastructures; governmental bodies; regulatory agencies; ethics committees; the pharmaceutical industry; and funding agencies. In addition, we searched websites of inter- or supranational bodies involved in clinical research until no further insights emerged. After consolidation of the identified definitions, concepts, and criteria of quality in a basic framework structure, we conducted 4 rounds of an adapted online Delphi process among the same 7 stakeholder groups from 16 countries. The Delphi process ultimately achieved consensus on structure and content. The framework addresses 5 study stages (concept, planning and feasibility, conduct, analysis and interpretation, and reporting and knowledge translation) and includes the following dimensions: (i) protection of patient safety and rights, (ii) relevance/patient centeredness and involvement, (iii) minimization of bias (internal validity), (iv) precision, (v) transparency/access to data, and (vi) generalizability (external validity) of study results. These dimensions interact with 2 promoters—infrastructure and sustainability through education—that include a set of factors that may enhance all listed quality dimensions. Each quality dimension contains specific questions and explanatory items that guide quality assessment at each research stage from conceptualization of the research question through reporting and knowledge translation of study results. In the last survey round, Delphi participants from 9 countries (Austria, Australia, Canada, Germany, Italy, the Netherlands, Switzerland, UK, and US) agreed on the structure, content, and wording of the research stages, quality dimensions, specific questions, and descriptive examples of the final framework. In Switzerland, INQUIRE has resulted in a roadmap that guides initiatives to increase value within the Swiss Clinical Trial Organization network and through affiliated researchers.ConclusionsWe present a framework based on a consensus of different stakeholder groups guiding the practical assessment of clinical research quality at all stages of a research project. Operationalization of this common structure will support the increase of value by guiding academic institutions and researchers in developing quality enhancement initiatives, from posing the right research question to the transparent publication of results.

2475 The leveling of clinical research competencies

OBJECTIVES/SPECIFIC AIMS: Objectives/goals: Describe the process used to develop leveled competencies and associated examples. Discuss the final leveled competencies and their potential use in clinical research professional workforce initiatives. METHODS/STUDY POPULATION: The revised JTFCTC Framework 2.0 has 51 competency statements, representing 8 domains. Each competency statement has now been refined to delineate fundamental, skilled or advanced levels of knowledge and capability. Typically, the fundamental level describes the competency for a professional that requires some coaching and oversight, but is able to understand and identify basic concepts. The skilled level of the competency reflects the professional’s solid understanding of the competency and use of the information to take action independently in most situations. The advanced level embodies high level thinking, problem solving, and the ability to guide others in the competency. The process for developing both the three levels and examples involved 5 workgroups, each chaired by a content expert and comprising of national/international clinical research experts, including representatives from research sites, professional associations, government, and industry and academic sponsors. RESULTS/ANTICIPATED RESULTS: The committee developed 51 specific competencies arrayed across 3 levels and examples of each to demonstrate an appropriate application of the competency. The competencies and examples, and potential utilization, will be described. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of competencies in the context of workforce development and training initiatives is helping to create standards for the clinical research profession. These leveled competencies allow for an important refinement to the standards that can be used to enhance the quality and safety of the clinical research enterprise and guide workforce development.