Opportunities and challenges in translational science

Abstract

American population remains frustratingly poor overall (4). This failure of translation is not for lack of effort; over $50B are spent on translational efforts in the public and private sectors every year. Opportunities for improvement abound: the cost of developing a new drug is now over $2B, continues to increase faster than inflation, and has increased relentlessly since 1950 despite enormous advances in science (5); the clinical trials process is widely acknowledged to be inefficient (6,7); after a drug or intervention is shown to be useful, its dissemination to all patients who could benefit is slow and variable (8,9), and patient adherence to those interventions remains suboptimal and limits the health benefits of the interventions developed (10). In all, the time required for the end-to-end translational process, from an idea in the lab to a drug or other intervention based on that idea reaching all patients who could benefit, is currently over 20 years, and its success rate is below 1%. Inspiring individual examples of remarkably effective therapies -including enzyme replacement therapies for particular rare diseases, small molecule correctors for cystic fibrosis, PCSK9 inhibitors for elevated cholesterol, and gene therapies for forms of inherited blindness and spinal muscular atrophy -demonstrate what a future therapeutic world might hold. But those successes remain the exceptions, with development times still measured in decades and resulting products having extremely high costs that are arguably unsustainable, and certainly undesirable. And while there have recently been some encouraging signs of improved overall timelines and success rates, productivity (success per unit of effort) and timelines have worsened over the last 40 years, in stark contrast to the remarkable increase in productivity in fundamental research during this time.These divergence have been recognized for some time (11,12), and a variety of efforts have been undertaken to address it. In the private sector, multiple mergers and acquisitions were undertaken in attempt to achieve economies of scale, and the multi-company collaborative TransCelerate Biopharma was formed in 2012 to create platforms for sharing among companies. Public-private partnerships, including the Innovative Medicines Initiative (IMI) in Europe, and the Accelerating Medicines Partnerships (AMP) in the U.S., have produced substantial datasets that are benefitting the entire research ecosystem. In the academic sector, the NIH Roadmap aimed to "redefine the ways that medical research is conducted and, ultimately, how research leads to improvements in health" (13). Among the Roadmap programs were several aimed at the translational divide. The Molecular Libraries Initiative (14) created a robust small molecule assay development, screening, and chemistry probe development capacity in the public sector for the first time, and was remarkably productive during its 10-year lifetime (15). The Clinical and Translational Science Awards (CTSA) program ( 16) has been similarly tra...

Valley of Death

“…10 With the increase in federal dollars to support basic science research, scientific discovery has outpaced translational science. 1 The NIH, for example, invests approximately $41.7 billion per year in medical research (http:// nih.gov/about-nih/what-we-do/budget), most of which is dedicated to basic science research. Therefore, scientists must rely on industry to translate their discoveries to clinical care.…”

“…In 2011, the NIH created the National Center for Advancing Translational Science. 1 Approximately 2% of the NIH budget was used to support the center in 2020. Through the Clinical and Translational Science Awards, the National Center for Advancing Translational Science has built a national network of medical research institutions to provide infrastructure to improve the success of translational research.…”

“…Through the Clinical and Translational Science Awards, the National Center for Advancing Translational Science has built a national network of medical research institutions to provide infrastructure to improve the success of translational research. 1 Services include support for clinical trials, biostatistics, informatics, regulatory support, and education. 1 Other funding agencies, including the Department of Defense, recognize the importance of translational research and have also developed translational research award programs.…”

“…Currently, the transfer of an innovative high-risk medical technology can take more than 2 decades, if it makes it at all. 1 ''Translational research'' is a relatively new concept, and it describes the process and science required to translate basic science discoveries to patient care. 8 The definition of translational research, however, is frequently misconstrued.…”

“…The National Institutes of Health (NIH) recently reported that the success rate of translating a laboratory discovery to patient care is \1%. 1 While ''discovery'' is a critical component of research, its value to society is lost if steps are not taken to translate these findings to the bedside. Thus, researchers, particularly those who are supported by taxpayer dollars, should do their best to initiate the steps to either translate the discovery to patient care or at least establish partnerships to help with the process of doing so.…”