Reproducibility, relevance and reliability as barriers to efficient and credible biomedical technology translation.

Biomedical research accuracy and relevance for improving healthcare are increasingly identified as costly problems. Basic research data quality, reporting and methodology, and reproducibility are common factors implicated in this challenge. Preclinical models of disease and therapy, largely conducted in rodents, have known deficiencies in replicating most human conditions. Their translation to human results is acknowledged to be poor for decades. Clinical data quality and quantity is also recognized as deficient; gold standard randomized clinical trials are expensive. Few solid conclusions from clinical studies are replicable and many remain unpublished. The translational pathway from fundamental biomedical research through to innovative solutions handed to clinical practitioners is therefore highly inefficient and costly in terms of wasted resources, early claims from fundamental discoveries never witnessed in humans, and few new, improved solutions available clinically for myriad diseases. Improving this biomedical research strategy and resourcing for reliability, translational relevance, reproducibility and clinical impact requires careful analysis and consistent enforcement at both funding and peer review levels.

Analysing the attributes of Comprehensive Cancer Centres and Cancer Centres across Europe to identify key hallmarks.

There is a persistent variation in cancer outcomes among and within European countries suggesting (among other causes) inequalities in access to or delivery of high-quality cancer care. European policy (EU Cancer Mission and Europe's Beating Cancer Plan) is currently moving towards a mission-oriented approach addressing these inequalities. In this study, we used the quantitative and qualitative data of the Organisation of European Cancer Institutes' Accreditation and Designation Programme, relating to 40 large European cancer centres, to describe their current compliance with quality standards, to identify the hallmarks common to all centres and to show the distinctive features of Comprehensive Cancer Centres. All Comprehensive Cancer Centres and Cancer Centres accredited by the Organisation of European Cancer Institutes show good compliance with quality standards related to care, multidisciplinarity and patient centredness. However, Comprehensive Cancer Centres on average showed significantly better scores on indicators related to the volume, quality and integration of translational research, such as high-impact publications, clinical trial activity (especially in phase I and phase IIa trials) and filing more patents as early indicators of innovation. However, irrespective of their size, centres show significant variability regarding effective governance when functioning as entities within larger hospitals.

Examining partnerships within an international knowledge translation network focused on youth mental health promotion.

BACKGROUND: Systems transformation for health promotion, involving engagement from multiple disciplines and levels of influence, requires an investment in partnership development. Integrated youth service is a collaborative model that brings organisations together to provide holistic care for youth. Frayme is an international knowledge translation network designed to support the uptake and scaling of integrated youth service. Social network analysis (SNA) is the study of relationships among social units and is useful to better understand how partners collaborate within a network to achieve major objectives. The purpose of this paper is to apply SNA to the Frayme network in order to (1) examine the level and strength of partnerships, (2) identify the strategies being employed to promote the main objectives and (3) apply the findings to current research in youth mental health and system transformation. METHODS: The PARTNER tool includes a validated survey and analysis software designed to examine partner interconnections. This tool was used to perform the SNA and 51 of the 75 partners completed the survey (14 researchers, 2 advisory groups and 35 organisations). A network map was created and descriptive frequencies were calculated. RESULTS: The overall network scores for the Frayme network were 20.6% for density, 81.5% for centralisation and 71.7% for overall trust. The Frayme secretariat received a 3.84 out of a possible 4 for value. In addition, the youth and family advisories each received a value score of 4 and all Leadership Team organisations received a score of 2.97 or above. CONCLUSIONS: The Frayme secretariat links many partners who would otherwise be disconnected and acts as a significant conduit for novel information. Frayme may have the opportunity to enhance value perceptions among broader network members by profiling individual organisations and the potential leveraging opportunities that might exist through their work. These findings increase understanding with respect to the mechanisms of network development and will be helpful to inform partnership development in the future. In addition, they contribute to the literature with respect to knowledge translation practice as well as the scaling of collaborative interventions within youth mental health.

Using a 'rich picture' to facilitate systems thinking in research coproduction.

BACKGROUND: In coproduction research, traditional 'end-users' are involved in the entire research process. The aim is to facilitate research translation by improving the timeliness and relevance of research. Because end-users often come from multiple sectors and hold diverse perspectives and priorities, involving them in coproduction can be challenging. Tools and approaches are needed to support coproduction teams to successfully navigate divergent viewpoints while producing rigorous but meaningful research outcomes. Rich pictures are a systems thinking tool to help make sense of complexity. In this paper, we describe how we developed and applied a 'rich picture' in a coproduction project with policy-level partners. METHODS: Guided by systems thinking principles, we conducted a systemic analysis of ethnographic fieldnotes collected as part of a broader study that examined the dynamics between an IT system and the implementation of the state-wide childhood obesity prevention programmes it was designed to monitor. Translating qualitative themes into metaphor and imagery, we created a visual depiction of the system to reflect the experience of the system's users (health promotion practitioners) and facilitated a workshop with policy-level programme administrators (i.e. participants, n = 7). Our aim was to increase the transparency of the system for our research partners and to spark new insights to improve the quality of programme implementation. RESULTS: Guided by provocative questions, participants discussed and challenged each other's thinking on the current functioning of the system. They identified future lines of inquiry to explore for quality improvement. Participants strongly agreed that the picture was a constructive way to engage with the ethnographic data but were challenged by the information and its implications. The opportunity for participants to co-learn from each other as well as from the picture was an added value. CONCLUSION: In the context of the facilitated workshop, the rich picture enabled research partners to engage with complex research findings and gain new insights. Its value was harnessed via the guided participatory process. This demonstrates the importance that, in the future, such tools should be accompanied by practices that enable participants to think with and apply systems thinking concepts and principles.

A mixed-methods approach to understanding partnership experiences and outcomes of projects from an integrated knowledge translation funding model in rehabilitation.

BACKGROUND: Integrated knowledge translation (IKT) can optimize the uptake of research evidence into clinical practice by incorporating knowledge users as equal partners in the entire research process. Although several studies have investigated stakeholder involvement in research, the literature on partnerships between researchers and clinicians in rehabilitation and their impact on clinical practice is scarce. This study described the individual research projects, the outcomes of these projects on clinical practice and the partnership experiences of an initiative that funds IKT projects co-led by a rehabilitation clinician and a researcher. METHODS: This was a sequential explanatory mixed methods study where quantitative data (document reviews and surveys) informed the qualitative phase (focus groups with researchers and interviews with clinicians). Descriptive analysis was completed for the quantitative data and thematic analysis was used for the qualitative data. RESULTS: 53 projects were classified within multiple steps of the KTA framework. Descriptive information on the projects and outcomes were obtained through the survey for 37 of the 53 funded projects (70%). Half of the respondents (n = 18) were very satisfied or satisfied with their project's impact. Only two (6%) projects reported having measured sustainability of their projects and four (11%) measured long-term impact. A focus group with six researchers and individual interviews with nine clinicians highlighted the benefits (e.g. acquired collaborative skills, stronger networks between clinicians and academia) and challenges (e.g. measuring KT outcomes, lack of planning for sustainability, barriers related to clinician involvement in research) of participating in this initiative. Considerations when partnering on IKT projects included: the importance of having a supportive organization culture and physical proximity between collaborators, sharing motives for participating, leveraging everyone's expertise, grounding projects in KT models, discussing feasibility of projects on a restricted timeline, and incorporating the necessary knowledge users. Clinicians discussed the main outputs (scientific contribution, training and development, increased awareness of best practice, step in a larger effort) as project outcomes, but highlighted the complexity of measuring outcomes on clinical practice. CONCLUSION: The study provides a portrait of an IKT funding model, sheds light on past IKT projects' strengths and weaknesses and provides strategies for promoting positive partnership experiences between researchers and rehabilitation clinicians.

The Italian Network for Tumor Bio-Immunotherapy (NIBIT) Foundation: ongoing and prospective activities in immuno-oncology.

The ongoing revolution in cancer immunotherapy stems from the knowledge that distinct immune-checkpoints regulate the physiological crosstalk between and among immune cells by delivering inhibitory or activating signals. These notions, and the availability of mAb directed to diverse immune-checkpoint molecules, have led to a significant clinical improvement in cancer treatment. In this scenario, further achievements are undoubtedly to be expected from the contribution of novel, proof-of-principle clinical trials designed to explore the therapeutic efficacy of new immunotherapy-based combinations and treatment sequences. Along these lines, the clinical translation of pre-clinical evidence generated by non-profit research entities is likely to provide a significant contribution to gaining new insights that will further boost the field of cancer immunotherapy. To pursue this goal, and to provide comprehensive educational programs in immune-oncology (I-O), several national and global networks have been revitalized or newly established in recent years. This rapidly evolving scenario led the Board of Directors of the Italian Network of Tumor Bio-Immunotherapy (NIBIT) to establish the NIBIT Foundation. This Focused Research Review summarizes the main ongoing and prospective I-O activities of the NIBIT Foundation.

Medical cannabis: aligning use to evidence-based medicine approach.

During the past decade we have been witnessing a rise in medical cannabis use, yet the evidence for the safety and efficacy of the various cannabinoid compounds is scarce. The State of Israel has always been at the forefront of clinical and translational research in support of Evidence Based Medicine. With respect to cannabis Israel has created a medical and regulatory environment that enables clinical studies with cannabis which may lead to improved Evidence Based use of these compounds. This opinion paper discusses selected studies into the safety and effects of cannabis derived products.

A change roadmap towards research paradigm in low-resource countries: retinoblastoma model in Egypt.

Research on childhood diseases represents a great global challenge. This challenge is maximized in both childhood cancer disciplines and developing world. In this paper, we aim at describing our institution experience in starting a structured childhood cancer research program in one of the developing countries in a short time based on philanthropic efforts. We used retinoblastoma as an example for what was conducted in this program. Starting in 2008, this program included improving clinical practice and its related supporting services besides developing new research services that both complement the clinical activities and pave the way towards creating a research foundation in the country. Results included developing hospital standard treatment protocols, developing national clinical trials, joining international consortia for childhood cancers clinical trials, developing data collection tools and real-time analytics, establishing a biobanking facility, and developing highly qualified team for conducting clinical, epidemiologic, and translational research studies. Moreover, this effort resulted in improving both clinical practice and patients' awareness nationally. This model can be used for other startup facilities that aim at finding answers for their national health problems in low-resource setting.

Promoting Cancer Control in Africa With "Ubuntu": A Report of the African Organization for Research and Training in Africa (AORTIC) 10th Conference, 2015 in Marrakech, Morocco.

The objectives of the African Organization for Research and Training in Cancer (AORTIC), includes bringing products of decades of advances in cancer research to African populations through local and international collaboration. The consistent and huge growth in participation in the conferences and the diversity of the nations is a witness to the success of the organization thus far. The theme for the Tenth AORTIC International Conference on Cancer in Africa in Morocco in 2015 was "Road map to Cancer Control in Africa" and topics of discussion of paramount importance for low- and middle-income African countries included childhood cancers such as BL, cancers of the cervix, breast, and prostate; cancers associated with HIV-infection such as cervical, vulvar, and anal; as well as cancer care challenges associated with palliative care. The role of environmental factors that underlie some epigenetic changes in some of the cancers was emphasized. Oral and poster presentations from various parts of the continent indicate the growth of basic and translational science of cancer in the region, with studies revealing regional diversity in the frequencies of the triple-negative breast cancer, cervical cancer, prostate cancer, HCC, and Burkitt's lymphoma. There was a sign that Africa is trying to keep pace with the paradigm shift and focusing on translational medicine. This was shown by suggestions for application of genome-wide association studies, new generation sequencing, as well as the evaluation of single nucleotide polymorphisms that may be responsible for variable susceptibility in some of the prevalent cancers in people of African descent. J. Cell. Physiol. 232: 2287-2295, 2017. © 2016 Wiley Periodicals, Inc.

New horizons in the implementation and research of comprehensive geriatric assessment: knowing, doing and the 'know-do' gap.

In this paper, we outline the relationship between the need to put existing applied health research knowledge into practice (the 'know-do gap') and the need to improve the evidence base (the 'know gap') with respect to the healthcare process used for older people with frailty known as comprehensive geriatric assessment (CGA). We explore the reasons for the know-do gap and the principles of how these barriers to implementation might be overcome. We explore how these principles should affect the conduct of applied health research to close the know gap. We propose that impaired flow of knowledge is an important contributory factor in the failure to implement evidence-based practice in CGA; this could be addressed through specific knowledge mobilisation techniques. We describe that implementation failures are also produced by an inadequate evidence base that requires the co-production of research, addressing not only effectiveness but also the feasibility and acceptability of new services, the educational needs of practitioners, the organisational requirements of services, and the contribution made by policy. Only by tackling these issues in concert and appropriate proportion, will the know and know-do gaps for CGA be closed.

Usefulness of a KT Event to Address Practice and Policy Gaps Related to Integrated Care.

There are limited evaluations of the impact of knowledge translation (KT) activities aimed at addressing practice and policy gaps. We report on the impact of an interactive, end-of-grant KT event. Although action items were developed and key stakeholder support attained, minimal follow-through had occurred three months after the KT event. Several organizational obstacles to transitioning knowledge into action were identified: leadership, program policies, infrastructure, changing priorities, workload and physician engagement. Key messages include: (1) ensure ongoing and facilitated networking opportunities, (2) invest in building implementation capacity, (3) target multi-level implementation activities and (4) focus further research on KT evaluation.

Maternal immunization efforts of the National Institutes of Health.

Over the last 35 years, efforts at the National Institutes of Health (NIH) to protect mothers and their infants against infectious diseases have involved a bench-to-bedside approach. Basic and translational research that provided a foundation for clinical trials of vaccines in pregnancy include natural history and vaccine antigen identification studies. Development of laboratory assays and reagents have been funded by NIAID; these are critical for the advancement of vaccine candidates through the preclinical and clinical steps along the maternal immunization research pathway to support vaccine efficacy. Animal models of maternal immunization have been developed to evaluate efficacy of vaccine candidates. Clinical studies required development of maternal immunization protocols to address specific pregnancy related issues, for enrollment and safety assessment of mothers and their infants. NIH has organized and participated in meetings, workshops and other collaborative efforts with partners have advanced maternal immunization efforts. Partners have included many institutes and offices at NIH as well as other Department of Health and Human Services agencies and offices (Food and Drug Administration, Centers for Disease Control and Prevention, National Vaccine Program Office), World Health Organization, academic investigators, Biotech and pharmaceutical companies, and nonprofit organizations such as the Bill and Melinda Gates Foundation. These research and development partnership are essential for advancing maternal immunization. Continued efforts are needed to promote maternal immunization to protect pregnant women and their infants against vaccine-preventable infectious disease, especially in resource-limited settings where the burden of infections is high.

Future translational applications from the contemporary genomics era: a scientific statement from the American Heart Association.

The field of genetics and genomics has advanced considerably with the achievement of recent milestones encompassing the identification of many loci for cardiovascular disease and variable drug responses. Despite this achievement, a gap exists in the understanding and advancement to meaningful translation that directly affects disease prevention and clinical care. The purpose of this scientific statement is to address the gap between genetic discoveries and their practical application to cardiovascular clinical care. In brief, this scientific statement assesses the current timeline for effective translation of basic discoveries to clinical advances, highlighting past successes. Current discoveries in the area of genetics and genomics are covered next, followed by future expectations, tools, and competencies for achieving the goal of improving clinical care.

Fast tracking the design of theory-based KT interventions through a consensus process.

BACKGROUND: Despite available evidence for optimal management of spinal pain, poor adherence to guidelines and wide variations in healthcare services persist. One of the objectives of the Canadian Chiropractic Guideline Initiative is to develop and evaluate targeted theory- and evidence-informed interventions to improve the management of non-specific neck pain by chiropractors. In order to systematically develop a knowledge translation (KT) intervention underpinned by the Theoretical Domains Framework (TDF), we explored the factors perceived to influence the use of multimodal care to manage non-specific neck pain, and mapped behaviour change techniques to key theoretical domains. METHODS: Individual telephone interviews exploring beliefs about managing neck pain were conducted with a purposive sample of 13 chiropractors. The interview guide was based upon the TDF. Interviews were digitally recorded, transcribed verbatim and analysed by two independent assessors using thematic content analysis. A 15-member expert panel formally met to design a KT intervention. RESULTS: Nine TDF domains were identified as likely relevant. Key beliefs (and relevant domains of the TDF) included the following: influence of formal training, colleagues and patients on clinicians (Social Influences); availability of educational material (Environmental Context and Resources); and better clinical outcomes reinforcing the use of multimodal care (Reinforcement). Facilitating factors considered important included better communication (Skills); audits of patients' treatment-related outcomes (Behavioural Regulation); awareness and agreement with guidelines (Knowledge); and tailoring of multimodal care (Memory, Attention and Decision Processes). Clinicians conveyed conflicting beliefs about perceived threats to professional autonomy (Social/Professional Role and Identity) and speed of recovery from either applying or ignoring the practice recommendations (Beliefs about Consequences). The expert panel mapped behaviour change techniques to key theoretical domains and identified relevant KT strategies and modes of delivery to increase the use of multimodal care among chiropractors. CONCLUSIONS: A multifaceted KT educational intervention targeting chiropractors' management of neck pain was developed. The KT intervention consisted of an online education webinar series, clinical vignettes and a video underpinned by the Brief Action Planning model. The intervention was designed to reflect key theoretical domains, behaviour change techniques and intervention components. The effectiveness of the proposed intervention remains to be tested.

Computational and experimental advances in drug repositioning for accelerated therapeutic stratification.

Drug repositioning is an important component of therapeutic stratification in the precision medicine paradigm. Molecular profiling and more sophisticated analysis of longitudinal clinical data are refining definitions of human diseases, creating needs and opportunities to re-target or reposition approved drugs for alternative indications. Drug repositioning studies have demonstrated success in complex diseases requiring improved therapeutic interventions as well as orphan diseases without any known treatments. An increasing collection of available computational and experimental methods that leverage molecular and clinical data enable diverse drug repositioning strategies. Integration of translational bioinformatics resources, statistical methods, chemoinformatics tools and experimental techniques (including medicinal chemistry techniques) can enable the rapid application of drug repositioning on an increasingly broad scale. Efficient tools are now available for systematic drug-repositioning methods using large repositories of compounds with biological activities. Medicinal chemists along with other translational researchers can play a key role in various aspects of drug repositioning. In this review article, we briefly summarize the history of drug repositioning, explain concepts behind drug repositioning methods, discuss recent computational and experimental advances and highlight available open access resources for effective drug repositioning investigations. We also discuss recent approaches in utilizing electronic health record for outcome assessment of drug repositioning and future avenues of drug repositioning in the light of targeting disease comorbidities, underserved patient communities, individualized medicine and socioeconomic impact.

Cancer Core Europe: a consortium to address the cancer care-cancer research continuum challenge.

European cancer research for a transformative initiative by creating a consortium of six leading excellent comprehensive cancer centres that will work together to address the cancer care-cancer research continuum. Prerequisites for joint translational and clinical research programs are very demanding. These require the creation of a virtual single 'e-hospital' and a powerful translational platform, inter-compatible clinical molecular profiling laboratories with a robust underlying computational biology pipeline, standardised functional and molecular imaging, commonly agreed Standard Operating Procedures (SOPs) for liquid and tissue biopsy procurement, storage and processing, for molecular diagnostics, 'omics', functional genetics, immune-monitoring and other assessments. Importantly also it requires a culture of data collection and data storage that provides complete longitudinal data sets to allow for: effective data sharing and common database building, and to achieve a level of completeness of data that is required for conducting outcome research, taking into account our current understanding of cancers as communities of evolving clones. Cutting edge basic research and technology development serve as an important driving force for innovative translational and clinical studies. Given the excellent track records of the six participants in these areas, Cancer Core Europe will be able to support the full spectrum of research required to address the cancer research- cancer care continuum. Cancer Core Europe also constitutes a unique environment to train the next generation of talents in innovative translational and clinical oncology.

Integrating quality improvement and translational research models to increase exclusive breastfeeding.

Exclusive breastfeeding (EBF), a perinatal core measure, is associated with a longer duration of breastfeeding. The purpose of this quality improvement project was to increase the percent of healthy term singleton newborns who were exclusively breastfed at an academic medical center in the Midwest. Implementation of skin-to-skin contact between mother and newborn immediately following birth resulted in an increase in the percent of healthy term singleton newborns who were EBF from 55% to 64%.

[Developing a tailored intervention: implementing recommendations for polypharmacy in multimorbid patients (PomP)]. / Entwicklung einer maßgeschneiderten Intervention (Tailoring) am Beispiel der Implementierung von Empfehlungen zur Polypharmakotherapie bei multimorbiden Patienten (PomP).

INTRODUCTION: Implementation research deals with the question of how to ensure that evidence-based knowledge is put into practice. One approach is the development of "tailored interventions (TI)". These are designed to address previously identified barriers and enablers. A common definition or methodological concept for TI has not yet been established. In this paper, a concept for TI is introduced. We describe the stepwise development of an implementation intervention for GP settings where recommendations based on current evidence are provided for the treatment of multimorbid patients receiving polypharmacy. Each step will be explained and illustrated by original data. METHODS/RESULTS: A stepwise approach was used to develop a TI: problem analysis, identification and prioritisation of determinants, identification and prioritisation of strategies and the design of a complex intervention and its underlying logic model. DISCUSSION: The stepwise exemplary description of this tailoring strategy may support other researchers in this field when designing a TI.