Evidence-Based Decision-Making 8: A Primer on Health Policy for Researchers.

There is a growing expectation that research will be used to inform decision-making. It is important for researchers to understand how health policy is developed and the different ways they can influence the development of policy.Public policy is developed to resolve identified problems. Health policy is a subset of public policy and is typically concerned with issues related to the health of populations either from a service delivery perspective or from a broader public health and social determinants of health perspective. The policy planning algorithm is well established and follows the basic decision-making framework: problem identification, policy formulation, implementation, and evaluation. A variety of government and nongovernment stakeholders engage in complex debates to identify and resolve policy issues. In this chapter, we explore how researchers can use their research to influence the development of health policy. Knowledge translation strategies focused on communicating research to policy-makers require considerable thought and planning.

DOHaD - the challenge of translating the science to policy.

The DOHaD Society has passed its 10th birthday, so it seems an appropriate time to reflect on what has been achieved and the Society's aspirations. At the 10th International Congress in Rotterdam in November 2017, Peter Gluckman (the Society's first President) delivered a plenary lecture entitled 'DOHaD - addressing the science-policy nexus: a reality check'; in opening the Congress, Mark Hanson (second, and outgoing President) not only highlighted the success of the Society but also the challenges it now faces in achieving impact for its work in the global health arena, that is beyond the research agenda; and in assuming the role of third President, Lucilla Poston highlighted the need for the Society to grasp opportunities to change healthcare policy, while persevering with basic research and well-planned intervention studies. In this review we summarize the points made in these three presentations and issue a call to action to the membership to take up the challenge of taking the Society's work to the next level of translating science to policy.

Prioritizing research challenges and funding for allergy and asthma and the need for translational research-The European Strategic Forum on Allergic Diseases.

The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision-makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real-world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients' organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics.

Biospecimens, Research Consent, and Distinguishing Cell Line Research.

Newly revised regulations for human research affecting translational oncology will become effective in January 2019. A substantial component of the debate leading to this revision was how to regulate biospecimen research; specifically, whether all biospecimens should be considered inherently "identifiable," thereby necessitating informed consent for use in research. The famous cases seminal to this discussion involve cancer cell lines, but the unique features of this kind of biospecimen research were largely missing from the regulatory deliberation. However, special aspects of cell line research-at the stages of procurement, generation, evolution, and sharing-alter how society should balance participant interests against the goals of research. Recommendations are offered to cancer researchers and policymakers going forward to enable ethically appropriate regulation of biospecimen research across its diverse spectrum.

Clinical translation of theranostic radiopharmaceuticals: Current regulatory status and recent examples.

With the development of ever more radiopharmaceuticals suitable for theranostic applications, translation of novel compounds from the preclinical stage towards clinical application becomes a bottleneck for the advances in Nuclear Medicine. This review article summarizes the current regulatory framework for clinical trials with radiopharmaceuticals in the European Union, provides a general overview of the documentation required, and addresses quality, safety, and clinical aspects to be considered. By using a recent successful example of translating a theranostic peptide radioligand, namely 111 In-CP04, which targets receptors expressed in medullary thyroid carcinoma, the pathway from the preclinical development over establishing the required pharmaceutical documentation to designing and submitting a clinical trial is reviewed. Details regarding preclinical data, generation of the documentation, and final successful application are described. This article should provide an insight in an ever more complex process to bring innovations in the field of radiopharmaceuticals into patients.

Surviving in the Valley of Death: Opportunities and Challenges in Translating Academic Drug Discoveries.

With pharmaceutical companies shrinking their research departments and exiting out of efforts related to unprofitable diseases, society has become increasingly dependent on academic institutions to perform drug discovery and early-stage translational research. Academic drug discovery and translational research programs assist in shepherding promising therapeutic opportunities through the so-called valley of death in the hope that a successful new drug will result in saved lives, improved health, economic growth, and financial return. We have interviewed directors of 16 such academic programs in the United States and found that these programs and the projects therein face numerous challenges in reaching the clinic, including limited funding, lack of know-how, and lack of a regional drug development ecosystem. If these issues can be addressed through novel industry partnerships, the revision of government policies, and expanded programs in translational education, more effective new therapies are more likely to reach patients in need.

A European regulatory perspective on cystic fibrosis: current treatments, trends in drug development and translational challenges for CFTR modulators.

In this article we analyse the current authorised treatments and trends in early drug development for cystic fibrosis (CF) in the European Union for the time period 2000-2016. The analysis indicates a significant improvement in the innovation and development of new potential medicines for CF, shifting from products that act on the symptoms of the disease towards new therapies targeting the cause of CF. However, within these new innovative medicines, results for CF transmembrane conductance regulator (CFTR) modulators indicate that one major challenge for turning a CF concept product into an actual medicine for the benefit of patients resides in the fact that, although pre-clinical models have shown good predictability for certain mutations, a good correlation to clinical end-points or biomarkers (e.g. forced expiratory volume in 1 s and sweat chloride) for all mutations has not yet been achieved. In this respect, the use of alternative end-points and innovative nonclinical models could be helpful for the understanding of those translational discrepancies. Collaborative endeavours to promote further research and development in these areas as well as early dialogue with the regulatory bodies available at the European competent authorities are recommended.

Introduction to the article collection 'Translation in healthcare: ethical, legal, and social implications'.

New technologies are transforming and reconfiguring the boundaries between patients, research participants and consumers, between research and clinical practice, and between public and private domains. From personalised medicine to big data and social media, these platforms facilitate new kinds of interactions, challenge longstanding understandings of privacy and consent, and raise fundamental questions about how the translational patient pathway should be organised.This editorial introduces the cross-journal article collection "Translation in healthcare: ethical, legal, and social implications", briefly outlining the genesis of the collection in the 2015 Translation in healthcare conference in Oxford, UK and providing an introduction to the contemporary ethical challenges of translational research in biology and medicine accompanied by a summary of the papers included in this collection.

Mesenchymal stromal cell-based therapy: Regulatory and translational aspects in gastroenterology.

The past decade has witnessed an outstanding scientific production focused towards the possible clinical applications of mesenchymal stromal cells (MSCs) in autoimmune and chronic inflammatory diseases. This raised the need of novel standards to adequately address quality, efficacy and safety issues of this advanced therapy. The development of a streamlined regulation is currently hampered by the complexity of analyzing dynamic biological entities rather than chemicals. Although numerous pieces of evidence show efficacy in reducing intestinal inflammation, some inconsistencies between the mechanisms of action of rodent vs human MSCs suggest caution before assigning translational value to preclinical studies. Preliminary evidence from clinical trials showed efficacy of MSCs in the treatment of fistulizing Crohn's disease (CD), and preparations of heterologous MSCs for CD treatment are currently tested in ongoing clinical trials. However, safety issues, especially in long-term treatment, still require solid clinical data. In this regard, standardized guidelines for appropriate dosing and methods of infusion could enhance the likelihood to predict more accurately the number of responders and the duration of remission periods. In addition, elucidating MSC mechanisms of action could lead to novel and more reliable formulations such as those derived from the MSCs themselves (e.g., supernatants).

Adapting Preclinical Benchmarks for First-in-Human Trials of Human Embryonic Stem Cell-Based Therapies.

UNLABELLED: : As research on human embryonic stem cell (hESC)-based therapies is moving from the laboratory to the clinic, there is an urgent need to assess when it can be ethically justified to make the step from preclinical studies to the first protocols involving human subjects. We examined existing regulatory frameworks stating preclinical requirements relevant to the move to first-in-human (FIH) trials and assessed how they may be applied in the context of hESC-based interventions to best protect research participants. Our findings show that some preclinical benchmarks require rethinking (i.e., identity, purity), while others need to be specified (i.e., potency, viability), owing to the distinctive dynamic heterogeneity of hESC-based products, which increases uncertainty and persistence of safety risks and allows for limited predictions of effects in vivo. Rethinking or adaptation of how to apply preclinical benchmarks in specific cases will be required repeatedly for different hESC-based products. This process would benefit from mutual learning if researchers included these components in the description of their methods in publications. SIGNIFICANCE: To design translational research with an eye to protecting human participants in early trials, researchers and regulators need to start their efforts at the preclinical stage. Existing regulatory frameworks for preclinical research, however, are not really adapted to this in the case of stem cell translational medicine. This article reviews existing regulatory frameworks for preclinical requirements and assesses how their underlying principles may best be applied in the context of human embryonic stem cell-based interventions for the therapy of Parkinson's disease. This research will help to address the question of when it is ethically justified to start first-in-human trials in stem cell translational medicine.

NCCN Work Group Report: Emerging Issues in Tissue Allocation.

Expanding research interests in molecular profiling over the past several years have led researchers in academia and pharmaceutical and biotechnology companies to significantly increase their need for access to tissue specimens collected through clinical care and clinical trials. As a result, tissue allocation has become a growing issue for many clinical and translational investigators. High-quality biospecimens are needed by all stakeholders in order to have scientifically accurate studies and results. At the center of the process are the patients, who have increasingly become active partners in the clinical research enterprise as individuals and through highly sophisticated patient advocacy organizations. All stakeholders must recognize that human specimens, including tissue, represent a valuable and unique resource that must have proper acquisition, handling, custodianship, and consent for use in accordance with best practices for biospecimen resources.

Sharing and Reuse of Sensitive Data and Samples: Supporting Researchers in Identifying Ethical and Legal Requirements.

Availability of and access to data and biosamples are essential in medical and translational research, where their reuse and repurposing by the wider research community can maximize their value and accelerate discovery. However, sharing human-related data or samples is complicated by ethical, legal, and social sensitivities. The specific ethical and legal requirements linked to sensitive data are often unfamiliar to life science researchers who, faced with vast amounts of complex, fragmented, and sometimes even contradictory information, may not feel competent to navigate through it. In this case, the impulse may be not to share the data in order to safeguard against unintentional misuse. Consequently, helping data providers to identify relevant ethical and legal requirements and how they might address them is an essential and frequently neglected step in removing possible hurdles to data and sample sharing in the life sciences. Here, we describe the complex regulatory context and discuss relevant online tools-one which the authors co-developed-targeted at assisting providers of sensitive data or biosamples with ethical and legal questions. The main results are (1) that the different approaches of the tools assume different user needs and prior knowledge of ethical and legal requirements, affecting how a service is designed and its usefulness, (2) that there is much potential for collaboration between tool providers, and (3) that enriched annotations of services (e.g., update status, completeness of information, and disclaimers) would increase their value and facilitate quick assessment by users. Further, there is still work to do with respect to providing researchers using sensitive data or samples with truly 'useful' tools that do not require pre-existing, in-depth knowledge of legal and ethical requirements or time to delve into the details. Ultimately, separate resources, maintained by experts familiar with the respective fields of research, may be needed while-in the longer term-harmonization and increase in ease of use will be very desirable.

A Plan for Academic Biobank Solvency-Leveraging Resources and Applying Business Processes to Improve Sustainability.

Researcher-initiated biobanks based at academic institutions contribute valuable biomarker and translational research advances to medicine. With many legacy banks once supported by federal funding, reductions in fiscal support threaten the future of existing and new biobanks. When the Brain Bank at Duke University's Bryan Alzheimer's Disease Center (ADRC) faced a funding crisis, a collaborative, multidisciplinary team embarked on a 2-year biobank sustainability project utilizing a comprehensive business strategy, dedicated project management, and a systems approach involving many Duke University entities. By synthesizing and applying existing knowledge, Duke Translational Medicine Institute created and launched a business model that can be adjusted and applied to legacy and start-up academic biobanks. This model provides a path to identify new funding mechanisms, while also emphasizing improved communication, business development, and a focus on collaborating with industry to improve access to biospecimens. Benchmarks for short-term Brain Bank stabilization have been successfully attained, and the evaluation of long-term sustainability metrics is ongoing.

Better safe than sorry: ethics review in European Union-funded health research.

Public scrutiny and the increasing number of projects addressing later stages of the research and innovation process announced the need for an enhanced attention to be paid to identify and address ethics concerns. Ex-ante ethics review as implemented in EU-funded health research and a proactive ethics management are a genuinely useful exercise and ensures top-quality research, from the lab to the patient.