Phases Of Translational Research Research Articles

From book to bedside? A critical perspective on the debate about "translational bioethics".

The concept of "translational bioethics" has received considerable attention in recent years. Most publications draw an analogy to translational medicine and describe bioethical research that aims at implementing and evaluating ethical interventions. However, current accounts of translational bioethics are often rather vague and seem to differ with regard to conceptual and methodological assumptions. It is not clear and scarcely analyzed what exactly "translation" in the field of bioethics means, in particular regarding goals and processes so that it is justified to appeal to translational medicine. In this article, we thus explore possible analogies and disanalogies between translational medicine and translational bioethics to establish whether the often occurring reference to concepts of translational medicine in the field of bioethics can be justified by substantial analogies. We will first provide an account of different models of translational medicine. In a second step, we will propose an analytic definition that explicitly articulates the essential characteristics of "translational research" irrespective of the research field (i.e., biomedicine, bioethics). Subsequently, we will explore whether and in how far general characteristics and phases of translational research in medicine can be applied to translational research in bioethics. Based on our analyses, we will come to the skeptical conclusion that at present there are considerable conceptual disanalogies and unsolved conceptual problems that disallow using "translational bioethics" in a meaningful analogy to respective accounts in biomedicine. Nevertheless, we will demonstrate that some insights gained by the conceptual accounts of translational medicine can contribute to advance current research activities in bioethics.

Bioethical Aspects of Translational Medicine

The development of modern medicine is associated with the dynamic translation (transfer) of basic medicine data to clinical research and further on to clinical practice. It is pointed out that research and development in the sphere of genetics and biotechnology, which are of particular significance during the COVID-19 pandemic, are of paramount importance in this regard. The concept of “translational distance” is analyzed as a measure of uncertainty, namely, the number and the size of logical leaps in course of transition from animal model trials to the first stages of human subject research. Translational research ethics has become a revolutionary, diverse, and distinct field of biomedical ethics. When studying the issue, special consideration is given to the critical blocks in translation as well as the characteristic features, types, and phases of translational research. It is emphasized that addressing the issue of minimizing irreducible uncertainty so that research participants could participate in research is a key component of ethical research. In view of the fact that the most important condition for the successful implementation of translational medicine is the adherence to the principles of bioethics when overcoming translational distances is analyzed taking into account the benefit-risk balance. As the development of translational medicine is significantly influenced by the legislation and the practice of its application, the national peculiarities of the attitude of different countries to the issues of ethics and the resolution thereof are studied, including the differences between the continental and the Anglo-Saxon legal families. Along with the formation of a general approach to the choice of a regulatory model in the sphere under consideration, the acceleration of circulation of the information related to science, research and technology, as well as the rapid obsolescence of innovations, should not be overlooked. At the same time, one should pay attention to the existing biological and other risks.

Clinical and translational science award T32/TL1 training programs: program goals and mentorship practices.

A national survey characterized training and career development for translational researchers through Clinical and Translational Science Award (CTSA) T32/TL1 programs. This report summarizes program goals, trainee characteristics, and mentorship practices. A web link to a voluntary survey was emailed to 51 active TL1 program directors and administrators. Descriptive analyses were performed on aggregate data. Qualitative data analysis used open coding of text followed by an axial coding strategy based on the grounded theory approach. Fifty out of 51 (98%) invited CTSA hubs responded. Training program goals were aligned with the CTSA mission. The trainee population consisted of predoctoral students (50%), postdoctoral fellows (30%), and health professional students in short-term (11%) or year-out (9%) research training. Forty percent of TL1 programs support both predoctoral and postdoctoral trainees. Trainees are diverse by academic affiliation, mostly from medicine, engineering, public health, non-health sciences, pharmacy, and nursing. Mentor training is offered by most programs, but mandatory at less than one-third of them. Most mentoring teams consist of two or more mentors. CTSA TL1 programs are distinct from other NIH-funded training programs in their focus on clinical and translational research, cross-disciplinary approaches, emphasis on team science, and integration of multiple trainee types. Trainees in nearly all TL1 programs were engaged in all phases of translational research (preclinical, clinical, implementation, public health), suggesting that the CTSA TL1 program is meeting the mandate of NCATS to provide training to develop the clinical and translational research workforce.

Advancing health equity through CTSA programs: Opportunities for interaction between health equity, dissemination and implementation, and translational science.

Dissemination and implementation (D&I) science is dedicated to studying how to effectively translate and apply research in real-world contexts. There has been increasing interest in health equity within the D&I field to ensure the equitable implementation of evidence-based programs/practices across a range of diverse populations and settings. At the same time, health equity researchers recognize the potential of D&I science to promote the more widespread dissemination, implementation, and sustainment of evidence-based interventions to address health inequities. The National Center for Accelerating Clinical and Translational Science Clinical and Translational Science Award (CTSA) Program has been a champion for community engagement and translational scholarship in its mission to improve individual and population health. The overall CTSA infrastructure and resources within and among CTSA hubs are well-equipped to facilitate a health equity focus to D&I across the phases of translational research. This paper proposes a framework that demonstrates the interaction and opportunities between health equity and D&I science and highlights how CTSAs can support and facilitate wider efforts in translational research with a focus on equitable D&I.

Translational Research in Psoriasis.

Translational research is a coordinated process that converts scientific knowledge about diseases from basic research into the development of therapeutic or diagnostic procedures in order to improve public health. Recent insights into the pathogenesis of psoriasis have greatly promoted the rational development of new therapeutic approaches. The integration of genetic predisposition and pathogenetic events defined the cytokine cascade as a target for therapeutic interventions. Applying various phases of translational research has enabled development of novel therapies that combine high efficacy with convincing safety profiles, with important implications for public health.

Close to the bench as well as at the bedside: involving service users in all phases of translational research

The paper aims to develop a model of translational research in which service user and other stakeholder involvement are central to each phase. 'Translational' is the current medical buzzword: translational research has been termed 'bench to bedside' research and promises to fast-track biomedical advances in the service of patient benefit. Models usually conceive of translational research as a 'pipeline' that is divided into phases: the early phase is characterized as the province of basic scientists and laboratory-based clinical researchers; the later phases focus on the implementation, dissemination and diffusion of health applications. If service user involvement is mentioned, it is usually restricted to these later phases. The paper critically reviews existing literature on translational research and medicine. The authors develop a theoretical argument that addresses why a reconceptualization of translational research is required on scientific, ethical and pragmatic grounds. The authors reconceptualize the model of translational research as an interlocking loop rather than as a pipeline, one in which service user and other stakeholder involvement feed into each of its elements. The authors demonstrate that for the 'interlocking loop' model of translational research to be materialized in practice will require changes in how health research is structured and organized. The authors demonstrate the scientific, ethical and pragmatic benefits of involving service users in every phase of translational research. The authors' reconceptualized model of translational research contributes to theoretical and policy debates regarding both translational research and service user involvement.

Strengthening the Reporting of Genetic Risk Prediction Studies: The GRIPS Statement

The recent successes of genome-wide association studies and the promises of whole genome sequencing fuel interest in the translation of this new wave of basic genetic knowledge to health care practice. Knowledge about genetic risk factors may be used to target diagnostic, preventive, and therapeutic interventions for complex disorders based on a person's genetic risk, or to complement existing risk models based on classical nongenetic factors, such as the Framingham risk score for cardiovascular disease. Implementation of genetic risk prediction in health care requires a series of studies that encompass all phases of translational research,1,2 starting with a comprehensive evaluation of genetic risk prediction. With increasing numbers of discovered genetic markers that can be used in future genetic risk prediction studies, it is crucial to enhance the quality of the reporting of these studies, since valid interpretation could be compromised by the lack of reporting of key information. Information that is often missing includes details in the description of how the study was designed and conducted (eg, how genetic variants were selected and coded, how risk models or genetic risk scores were constructed, and how risk categories were chosen), or how the results should be interpreted. An appropriate assessment of the study's strengths and weaknesses is not possible without this information. There is ample evidence that prediction research often suffers from poor design and bias, and these may also have an impact on the results of the studies and on models of disease outcomes based on these studies.3–5 Although most prognostic studies published to date claim significant results,6,7 very few translate to clinically useful applications. Just as for observational epidemiological studies,8 poor reporting complicates the use of the specific study for research, clinical, or public health purposes and hampers the …

Policy Implications of the Society for Healthcare Epidemiology of America's Research Plan for Reducing Healthcare-Associated Infections

From the Division of Infectious Diseases, The Ohio State University College of Medicine, Columbus (K.B.S.), and the Department of Infectious Diseases, The Cleveland Clinic, Cleveland (S.G.), Ohio. Received December 11, 2009; accepted December 13, 2009; electronically published December 29, 2009. Infect Control Hosp Epidemiol 2010; 31:124-126 2009 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2010/3102-0003$15.00. DOI: 10.1086/650583 The country is currently in the midst of a healthcare debate about all aspects of healthcare spending; $2.4 trillion is spent annually on health care, representing 16% of the gross national product. The focus has been on value-based competition (paying for performance and not quantity of care) and on patient safety and the quality of medical care. Two seminal publications from the Institute of Medicine were early catalysts for the creation of this movement to reform healthcare spending: To Err is Human: Building a Safer Health System, published in 2000, and Crossing the Quality Chasm: A New Health System for the 21st Century, published in 2001. Infectious diseases physicians and healthcare epidemiologists were the first to point out that healthcare-associated infections (HAIs) were major contributors to adverse events associated with the delivery of health care. The focus on HAIs is in part because many of these infections are preventable and can be measured using standard and well-validated surveillance systems and definitions. Public health officials, government officials, and consumer advocates have recognized the impact of HAIs, as witnessed by the increased emphasis on legislation for the public reporting of HAIs. Furthermore, many HAIs are increasingly difficult to treat because of their consistent association with multidrug-resistant organisms (MDROs). The Centers for Disease and Prevention and the Healthcare Infection Control Practices Advisory Committee have provided guidance on infection control and prevention. Among national leaders in this arena, SHEA has been an advocate for active surveillance and prevention programs. A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals, published by SHEA, represents a compilation of evidence-based practices and expert consensus opinion on strategies to address the prevention of HAIs and the transmission of MDROs. Despite this exhaustive review of the current evidence, it has been increasingly clear that there are significant gaps in knowledge that require a broad and multifaceted research agenda to bridge. One timely example is the current debate on respiratory protection for healthcare workers against novel H1N1 influenza A virus in the workplace. The Institute of Medicine Committee, which is charged with studying this issue, reported on a recommendation for supporting the use of fittested N95 respirators and also increasing research on influenza transmission and personal respiratory protection. The article by the Research Committee of SHEA published in this issue of the journal outlines a comprehensive national research agenda on HAIs, addressing 3 major areas of research: pathogenesis, epidemiology, and infection prevention strategies. A fourth area of proposed research is in improving the design of healthcare epidemiology studies. Pathogenesis and host defense mechanisms have been the subject of much funding, provided by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH). Funding for the other areas of the proposed research agenda has been extremely limited, with clinical investigators in healthcare epidemiology and prevention implementation research receiving relatively less funding than colleagues in basic science disciplines. From a policy perspective, enhancing the funding for HAI research is at the core of the SHEA research agenda. The recent emphasis by the NIH on translational research is promising, because it recognizes the need to effectively implement, diffuse, and disseminate medical discoveries into clinical practice. The later phases of translational research (ie, phase 3 translation research and phase 4 translation research) focus on moving evidence-based practices into health

The Applicability of Lean and Six Sigma Techniques to Clinical and Translational Research

BackgroundLean and Six Sigma are business management strategies commonly used in production industries to improve process efficiency and quality. During the past decade, these process improvement techniques increasingly have been...

Public Health Genomics: Translating Obesity Genomics Research Into Population Health Benefits

We examine how a public health genomics framework can be used to move genomic discoveries into clinical and public health practice for obesity prevention and treatment. There are four phases of translational research: T1: discovery to candidate health application; T2: health application to evidence-based practice guidelines; T3: practice guidelines to health practice; and T4: practice to population health impact. Types of multidisciplinary research and knowledge synthesis needed for each phase, as well as the importance of developing and disseminating evidence-based guidelines, are discussed. Because obesity genomics research is mostly in the discovery phase or in the very early phases of translation (T1), the authors present this framework to illustrate the range of translation activities needed to move genomic discoveries in obesity to actual applications that reduce the burden of obesity at the population level.

Immunohistochemical assessment of protein phosphorylation state: the dream and the reality

The development of phosphorylation state-specific antibodies (PSSAs) in the 1980s, and their subsequent proliferation promised to enable in situ analysis of the activation states of complex intracellular signaling networks. The extent to which this promise has been fulfilled is the topic of this review. I review some applications of PSSAs primarily in the assessment of solid tumor signaling pathway activation status. PSSAs have received considerable attention for their potential to reveal cell type-specific activation status, provide added prognostic information, aid in the prediction of response to therapy, and most recently, demonstrate the efficacy of kinase-targeted chemotherapies. However, despite some successes, many studies have failed to demonstrate added value of PSSAs over general antibody immunohistochemistry. Moreover, there is still a large degree of uncertainty about the interpretation of complex and heterogeneous staining patterns in tissue samples and their relationship to the actual phosphorylation states in vivo. The next phase of translational research in applications of PSSAs will entail the hard work of antibody validation, gathering of detailed information about epitope-specific lability, and implementation of methods for standardization.

Psoriasis: evolution of pathogenic concepts and new therapies through phases of translational research

Psoriasis: evolution of pathogenic concepts and new therapies through phases of translational research

Psoriasis: evolution of pathogenic concepts and new therapies through phases of translational research

Psoriasis is perhaps unique for a disease studied through translational science in that there is not an accepted animal model, yet many rounds of bidirectional translation have taken place that have helped to define disease pathogenesis and to advance therapy. In this review, we illustrate the evolution of new pathogenic concepts and the testing of new therapeutic agents through translational research in humans. We present a current view of disease pathogenesis that stems from research in patients and animal models, but with the perspectives (i) that disease models can advance or hinder the overall translational enterprise and (ii) that the research process must be firmly grounded in the pathophysiology of the actual human condition.

Translational Research in Childhood Obesity Prevention

This article explores the state of translational research in childhood obesity prevention. Five phases of translational research and emerging findings from basic science that could be useful in the design of obesity prevention programs are described. Few intervention studies have been published, and these are dominated by Phase 3 trials (efficacy), conducted in school settings, with a limited number of studies finding significant effects on Body Mass Index or adiposity. Cost-benefit analyses are lacking. Research is needed to translate basic science findings into novel interventions (Phases 1 and 2) and to translate programs with known behavior change capability into dissemination trials (Phase 5). Translation can be facilitated by enhanced communication between basic science and prevention science researchers, the development of interventions for underused settings, using novel strategies, support by institutions and funding agencies for translation, and the design of interventions with translation in mind.