Health Care Evolves From Reactive to Proactive.

Decoding health and disease pathways drives healthcare evolution. Historically, therapeutic paradigms have relied on interventions that mitigate symptoms of established diseases. Increasingly, molecular insights into pathophysiology now provide unprecedented opportunities to offer curative solutions or even prevent disease and thereby secure longitudinal wellness. These opportunities extend past individual patients to entire populations and geographies. Moreover, they optimize prospective healthspan across lifespan. Linking discovery science and its translatable innovations beyond reactive disease intervention to proactive prevention will maximize society’s returns creating the greatest benefit for the greatest number of people globally

Clinical Pharmacology & Therapeutics: Past, Present, and Future.

Clinical Pharmacology & Therapeutics (CPT), the definitive and timely source for advances in human therapeutics, transcends the drug discovery, development, regulation, and utilization continuum to catalyze, evolve, and disseminate discipline-transformative knowledge. Prioritized themes and multidisciplinary content drive the science and practice of clinical pharmacology, offering a trusted point of reference. An authoritative herald across global communities, CPT is a timeless information vehicle at the vanguard of discovery, translation, and application ushering therapeutic innovation into modern healthcare

Process Improvement for Maximized Therapeutic Innovation Outcome.

Deconvoluting key biological mechanisms forms the framework for therapeutic discovery. Strategies that enable effective translation of those insights along the development and regulatory path ultimately drive validated clinical application in patients and populations. Accordingly, parity in What vs. How we transform novel mechanistic insights into therapeutic paradigms is essential in achieving success. Aligning molecular discovery with innovations in structures and processes along the discovery-development-regulation-utilization continuum maximizes the return on public and private investments for next-generation solutions in managing health and disease

Peer Review Certifies Quality and Innovation in Clinical Pharmacology & Therapeutics.

Clinical Pharmacology & Therapeutics (CPT) is an established voice of the discipline, a trusted source of new knowledge showcasing discovery, translation, and application of novel therapeutic paradigms to advance the management of patients and populations. Identifying, evaluating, prioritizing, and disseminating the best science along the discovery-development-regulatory-utilization continuum are responsibilities shared through peer review. To enhance the uniformity of this essential component of quality assurance and innovation, and maximize the value of the journal and its contents to authors, reviewers, and the readership, we review key concepts concerning peer review as it specifically relates to CPT

A study of microRNAs in silico and in vivo: diagnostic and therapeutic applications in cancer.

There is emerging evidence of the production in human tumors of abnormal levels of microRNAs (miRNAs), which have been assigned oncogenic and/or tumor-suppressor functions. While some miRNAs commonly exhibit altered amounts across tumors, more often, different tumor types produce unique patterns of miRNAs, related to their tissue of origin. The role of miRNAs in tumorigenesis underscores their value as mechanism-based therapeutic targets in cancer. Similarly, unique patterns of altered levels of miRNA production provide fingerprints that may serve as molecular biomarkers for tumor diagnosis, classification, prognosis of disease-specific outcomes and prediction of therapeutic responses

The value proposition of molecular medicine.

Individualized patient management is rapidly evolving, driven by the emergence of insights in discovery, development, regulatory, and comparative effectiveness sciences.1-4 The pace of discovery is accelerating, enabled by platforms, including “omics”, stem cell biology, network medicine, and medical and biological informatics that provide unanticipated insights into pathophysiology.2, 4-6 The integration of these paradigms has established a model for identifying the mechanistic underpinnings of disease, offering novel opportunities to individualize diagnostics that shape how modern therapies are deployed, including markers of disease prognosis, clinical predictors of therapeutic responses, and molecular determinants that optimize clinical management.7-10 Importantly, deconvolution of physiological circuits is producing a new vanguard of molecular therapies that target corrupted pathways at the center of disease pathogenesis, individualizing patient care algorithms that optimize benefits and minimize adverse effects

Managing the innovation supply chain to maximize personalized medicine.

Personalized medicine epitomizes an evolving model of care tailored to the individual patient. This emerging paradigm harnesses radical technological advances to define each patient\u27s molecular characteristics and decipher his or her unique pathophysiological processes. Translated into individualized algorithms, personalized medicine aims to predict, prevent, and cure disease without producing therapeutic adverse events. Although the transformative power of personalized medicine is generally recognized by physicians, patients, and payers, the complexity of translating discoveries into new modalities that transform health care is less appreciated. We often consider the flow of innovation and technology along a continuum of discovery, development, regulation, and application bridging the bench with the bedside. However, this process also can be viewed through a complementary prism, as a necessary supply chain of services and providers, each making essential contributions to the development of the final product to maximize value to consumers. Considering personalized medicine in this context of supply chain management highlights essential points of vulnerability and/or scalability that can ultimately constrain translation of the biological revolution or potentiate it into individualized diagnostics and therapeutics for optimized value creation and delivery

Clinical Translational Science 2020: Disruptive Innovation Redefines the Discovery-Application Enterprise

Vaccines, analgesia, and antibiotics embody some of the most enduring therapeutic breakthroughs that have transformed medicine. Building on such fine paradigms of biomedical innovation, the evolution of technologies has increasingly sparked spectacular advances across the continuum of wellness and disease-spanning medical and surgical specialties. Discovery science—fueled by government and private sector resources—has systematically instituted the principles of modern healthcare delivery ensuring that medical practice is based on up-to-date scientifi c evidence. Th e harmony between science, technology, and resources has culminated in a golden age of discovery and translation, eradicating infections, curing cancers, and palliating endocrine and metabolic diseases. Indeed, proven therapeutic and preventive approaches have progressively moved into everyday practice

Chronic diseases: the emerging pandemic.

According to the 2011 World Health Organization Global Status Report, of the 57 million annual global deaths – a staggering 36 million or over 63% are due to chronic diseases.1 Four noncommunicable diseases - namely cardiovascular, cancer, diabetes, and chronic respiratory diseases - emerge as the leading cause of mortality in the world, accounting respectively for 17, 7.6, 4.2, and 1.3 million deaths based on the latest available global epidemiology data. By 2020, global deaths due to chronic diseases are projected to worsen by at least 15 to 20%. It is estimated that the four major noncommunicable diseases will be responsible for 75% of worldwide deaths by 203

Sizing up pharmacotherapy for obesity.

Obesity has increased over the last 20 years, from a condition affecting only a small portion of populations in developed countries, into a global pandemic. The impact of obesity can be appreciated in the context of the populations at risk, and it is estimated that \u3e1 billion adults worldwide are overweight (BMI \u3e25 kg/m2), 300 million of whom are clinically obese (BMI \u3e30 kg/m2). In the United States, 65% of adults are overweight, and 32.2% of them are obese, a prevalence that has doubled over 20 years. In industrialized countries, obesity rates have tripled, coinciding with adoption of a Western lifestyle. Further, the growing worldwide rates of childhood obesity have reached epidemic values in developed countries. This global obesity pandemic reflects genetic susceptibility, availability of high-energy foods, and decreased physical activity. Accelerating rates of obesity have profound health and economic consequences. Obesity is associated with a myriad of co-morbidities, including type II diabetes, coronary artery disease, obstructive sleep apnea, stroke, cancer, hypertension, osteoarthritis, and liver and biliary disease which collectively increase mortality. Indeed, the health care impact of chronic obesity exceeds that of smoking or alcohol abuse. National health care costs of obesity are $70-100 billion, and if this trend continues, in 15 years 20% of health care costs in the United States will be attributed to the chronic diseases associated with obesity