Biomarkers are critical to the rational development of medical therapeutics, but significant confusion persists regarding fundamental definitions and concepts involved in their use in research and ...clinical practice, particularly in the fields of chronic disease and nutrition. Clarification of the definitions of different biomarkers and a better understanding of their appropriate application could result in substantial benefits. This review examines biomarker definitions recently established by the U.S. Food and Drug Administration and the National Institutes of Health as part of their joint Biomarkers, EndpointS, and other Tools (BEST) resource. These definitions are placed in context of their respective uses in patient care, clinical research, or therapeutic development. We explore the distinctions between biomarkers and clinical outcome assessments and discuss the specific definitions and applications of diagnostic, monitoring, pharmacodynamic/response, predictive, prognostic, safety, and susceptibility/risk biomarkers. We also explore the implications of current biomarker development trends, including complex composite biomarkers and digital biomarkers derived from sensors and mobile technologies. Finally, we discuss the challenges and potential benefits of biomarker-driven predictive toxicology and systems pharmacology, the need to ensure quality and reproducibility of the science underlying biomarker development, and the importance of fostering collaboration across the entire ecosystem of medical product development.
Impact statement
Biomarkers are critical to the rational development of medical diagnostics and therapeutics, but significant confusion persists regarding fundamental definitions and concepts involved in their use in research and clinical practice. Clarification of the definitions of different biomarker classes and a better understanding of their appropriate application could yield substantial benefits. Biomarker definitions recently established in a joint FDA-NIH resource place different classes of biomarkers in the context of their respective uses in patient care, clinical research, or therapeutic development. Complex composite biomarkers and digital biomarkers derived from sensors and mobile technologies, together with biomarker-driven predictive toxicology and systems pharmacology, are reshaping development of diagnostic and therapeutic technologies. An approach to biomarker development that prioritizes the quality and reproducibility of the science underlying biomarker development and incorporates collaborative regulatory science involving multiple disciplines will lead to rational, evidence-based biomarker development that keeps pace with scientific and clinical need.
The article discusses the key role that federal regulatory frameworks play in governing medical products to show how they benefit patients when used and ensure timely access to needed therapies and ...diagnostics. The role to be played by a National Evaluation System for Health Technology (NEST) is highlighted.
Summary Few trials of glucose-lowering drugs or strategies in people with type 2 diabetes have investigated cardiovascular outcomes, even though most patients die from cardiovascular causes despite ...the beneficial effects of lipid-reducing and blood pressure-lowering treatments. The evidence-based reduction in risk of microvascular disease with glucose lowering has resulted in guidelines worldwide recommending optimisation of glycosylated haemoglobin, but no trial results have shown unequivocal cardiovascular risk reduction with glucose lowering. However, results of the post-trial follow-up of the UK Prospective Diabetes Study, and of a meta-analysis of the four glucose-lowering outcome trials completed to date, suggest about a 15% cardiovascular relative risk reduction per 1% decrement in HbA1c . The 2008 US Food and Drug Administration industry guidance for licensing of antidiabetic drugs greatly increased the number of cardiovascular outcome trials in diabetes, but most trials opted for non-inferiority designs aiming primarily to show absence of cardiovascular toxicity in the shortest possible time. This unintended consequence of the new regulations has meant that the potential long-term benefits, and the possible risks of new therapies, are not being assessed effectively. Also, essential head-to-head trials of therapies for this complex progressive disease, to answer issues such as how best to achieve and maintain optimum glycaemia without promoting weight gain or hypoglycaemia, are not being undertaken. In this Series paper, we summarise randomised controlled cardiovascular outcome trials in type 2 diabetes, provide an overview of ongoing trials and their limitations, and speculate on how future trials could be made more efficient and effective.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The FDA has committed to working with other agencies, health care providers, industry, and patients and families to deal proactively with the opioid abuse crisis, while safeguarding appropriate ...access to vitally important pain medications for the patients who need them.
We at the Food and Drug Administration (FDA) continue to be deeply concerned about the growing epidemic of opioid abuse, addiction, and overdose — an epidemic directly related to the increasingly widespread misuse of powerful opioid pain medications. As the federal agency charged with ensuring that the drugs used by the U.S. public are both effective and safe, we are committed to working in partnership with other government agencies, health care providers, the medical products industry and, most important, patients and their families to deal proactively with this unfolding public health crisis, which has already profoundly affected individuals, families, and . . .
During the past year, clinicians and the public have been focused on the coronavirus disease 2019 (COVID-19) pandemic and its associated societal and economic effects. However, once the acute phase ...of this crisis has passed, we will face an enormous wave of death and disability as a result of common chronic diseases (CCDs), with cardiometabolic diseases at the crest (Figure). A tsunami results when an earthquake on the ocean floor creates huge waves that can wreak devastation far distant from the original upheaval, especially when warnings are ignored. Similarly, underlying global and national demographic and risk factor profiles have for some time presaged an overwhelming burden of CCDs. However, although the pandemic has created additional impetus that unless heeded will amplify the consequences of this burden, the rapid adaptations and innovations in care and research prompted by the urgent response to it may also offer us the means to stem this flood.
Previous decades have seen significant progress in the biological understanding of cardiovascular disease, as well as major advances in computational and information technologies. However, ...anticipated improvements in outcomes, quality, and cost of cardiovascular medicine at the individual and population levels from these advances have lagged expectations. Further, trends showing widening gaps in the pace of technological development and its successful uptake and application in practice suggests that substantial systemic changes are needed. Recent declines in key U.S. health outcomes have added further urgency to seek scalable approaches that deliver the right treatment to the right patient and to develop information-driven policies that improve health. The clinical care and research enterprises are currently in the midst of assimilating changes entrained by a "fourth industrial revolution" marked by the convergence of biology, physical sciences, and information science. These changes, if managed appropriately, can simultaneously enable cost-effective personalized medical care as well as more effective and targeted population health interventions. In this paper derived from a lecture in honor of cardiologist Paul Dudley White, the author explores how White's prescient insights into prevention and treatment continue to resonate today as we seek to assimilate ubiquitous computing, sophisticated sensor technologies, and bidirectional digital communication into the practice of cardiology. How the ongoing acceleration in basic science and information technologies can be wedded to the principles articulated by White as we pursue scalable approaches to personalized medicine is also examined.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although advances in care have spurred improvements in cardiovascular outcomes, cardiovascular disease remains the leading cause of death in the United States and around the world. Previous declines ...in cardiovascular disease mortality have slowed and even reversed for certain demographics. Further concerns exist with regard to cardiovascular drug innovation, quality of care, and healthcare costs. The Value in Healthcare Initiative–Transforming Cardiovascular Care, a collaboration of the American Heart Association and Duke University, Robert J. Margolis, MD, Center for Health Policy, aims to increase access to and affordability of cardiovascular treatment and to decrease barriers to care. The following Call to Action describes trends in cardiovascular care, identifies gaps in areas of cardiovascular disease prevention and treatment, highlights challenges with medical product innovation, and finally, outlines a series of learning collaboratives that will aid in the development of road maps for transforming cardiovascular care.
The FDA and the Clinical Community Califf, Robert M
JAMA : the journal of the American Medical Association,
09/2022, Volume:
328, Issue:
11
Journal Article
Peer reviewed
Open access
This Viewpoint from FDA Commissioner Robert Califf, MD, emphasizes the agency’s overarching priorities focused on helping to create a system that benefits from abundant high-quality evidence in a ...transparent environment.
The need for high-quality evidence to support decision making about health and health care by patients, physicians, care providers, and policy-makers is well documented. However, serious shortcomings ...in evidence persist. Pragmatic clinical trials that use novel techniques including emerging information and communication technologies to explore important research questions rapidly and at a fraction of the cost incurred by more “traditional” research methods promise to help close this gap. Nevertheless, while pragmatic clinical trials can bridge clinical practice and research, they may also raise difficult ethical and regulatory challenges. In this article, the authors briefly survey the current state of evidence that is available to inform clinical care and other health-related decisions and discuss the potential for pragmatic clinical trials to improve this state of affairs. They then propose a new working definition for pragmatic research that centers upon fitness for informing decisions about health and health care. Finally, they introduce a project, jointly undertaken by the National Institutes of Health Health Care Systems Research Collaboratory and the National Patient-Centered Clinical Research Network (PCORnet), which addresses 11 key aspects of current systems for regulatory and ethical oversight of clinical research that pose challenges to conducting pragmatic clinical trials. In the series of articles commissioned on this topic published in this issue of Clinical Trials, each of these aspects is addressed in a dedicated article, with a special focus on the interplay between ethical and regulatory considerations and pragmatic clinical research aimed at informing “real-world” choices about health and health care.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK, VSZLJ
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