A systems approach to enable effective team science from the internal research program of the National Center for Advancing Translational Sciences.

The internal research program of the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health aims to fundamentally transform the preclinical translational research process to get more treatments to more people more quickly. The program develops and implements innovative scientific and operational approaches that accelerate and enhance translation across many diverse projects. Cross-disciplinary team science is a defining feature of our organization, with scientists at all levels engaged in multiple research teams. Here, we share our systems approach to nurturing cross-disciplinary team science, which leverages organizational policies, structures, and processes. Policies including the organizational mission statement, principles for ethical conduct of research, performance review criteria, and training program objectives and approaches reinforce the value of team science to achieve the program's scientific goals. Structures including an organizational structure designed around solving translational problems, co-location of employees in a single state-of-the-art scientific facility, and shared-use laboratories, expertise and instrumentation facilitate collaboration. Processes including fluid team assembly, specialized project management, cross-agency partnerships, and decision making based on clear screening criteria and milestones enable effective team assembly and functioning. We share evidence of the impact of these approaches on the science and commercialization of findings and discuss pathways to broad adoption of similar approaches.

Collaborative development of 2-hydroxypropyl-ß-cyclodextrin for the treatment of Niemann-Pick type C1 disease.

In 2010, the National Institutes of Health (NIH) established the Therapeutics for Rare and Neglected Diseases (TRND) program within the National Center for Advancing Translational Sciences (NCATS), which was created to stimulate drug discovery and development for rare and neglected tropical diseases through a collaborative model between the NIH, academic scientists, nonprofit organizations, and pharmaceutical and biotechnology companies. This paper describes one of the first TRND programs, the development of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) for the treatment of Niemann-Pick disease type C1 (NPC1). NPC is a neurodegenerative, autosomal recessive rare disease caused by a mutation in either the NPC1 (about 95% of cases) or the NPC2 gene (about 5% of cases). These mutations affect the intracellular trafficking of cholesterol and other lipids, which leads to a progressive accumulation of unesterified cholesterol and glycosphingolipids in the CNS and visceral organs. Affected individuals typically exhibit ataxia, swallowing problems, seizures, and progressive impairment of motor and intellectual function in early childhood, and usually die in adolescence. There is no disease modifying therapy currently approved for NPC1 in the US. A collaborative drug development program has been established between TRND, public and private partners that has completed the pre-clinical development of HP-ß-CD through IND filing for the current Phase I clinical trial that is underway. Here we discuss how this collaborative effort helped to overcome scientific, clinical and financial challenges facing the development of new drug treatments for rare and neglected diseases, and how it will incentivize the commercialization of HP-ß-CD for the benefit of the NPC patient community.

Leveraging public private partnerships to innovate under challenging budget times.

The National Institutes of Health (NIH), academic medical centers and industry have a long and productive history in collaborating together. Decreasing R&D budgets in both the private and public sector have made the need for such collaborations paramount to reduce the risk of further declines in the number of innovative drugs reaching the market to address pressing public health needs. Doing more with less has forced both industry and public sector research institutions (PSRIs) to leverage resources and expertise in order to de-risk projects. In addition, it provides an opportunity to envision and implement new approaches to accomplish these goals. We discuss several of these innovative collaborations and partnerships at the NIH that demonstrate how the NIH and industry are working together to strengthen the drug development pipeline.

Advancing translational research collaborations.

In February 2010, the U.S. National Institutes of Health (NIH) sponsored a national Clinical and Translational Science Awards forum titled "Promoting Efficient and Effective Collaborations among Academia, Government and Industry." This forum brought together a broad set of stakeholders who were charged with developing a path for promoting such partnerships. Here, we describe key issues discussed at the forum and plans for moving forward with this ambitious agenda.

Reaping the benefits of biomedical research: partnerships required.

Reaping the benefits of investments in biomedical research can be achieved most efficiently through active collaboration among industry, academia, government, and nonprofit organizations. The National Institutes of Health (NIH) are exploring multiple ways in which to increase the efficiency of the translational process. Investigators involved in the NIH-funded Clinical and Translational Science Awards are developing public-private partnerships, addressing the barriers to collaboration, training the next generation of interdisciplinary team-oriented researchers, and producing open-source tools for collaboration. NIH is engaging with industry through the Foundation for the NIH and the Small Business Innovation Research Awards.

NIH conference on the future of telehealth: essential tools and technologies for clinical research and care--a summary. June 25-26, 2009 Bethesda, Maryland.

Major government efforts to widen the use of health information technology and speed the translation of biomedical research discoveries into clinical practice are converging with the rapid growth of the Internet to create unprecedented opportunities to use telehealth networks to broaden access to high-quality healthcare and expand the scope and reach of clinical and translational research. Recognizing the dual potential of telehealth networks to improve health outcomes and reduce barriers to participation in research, particularly in medically underserved communities, the National Center for Research Resources (NCRR), part of the National Institutes of Health (NIH), convened a national conference at the NIH on June 25-26, 2009, titled "Future of Telehealth: Essential Tools and Technologies for Clinical Research and Care," in collaboration with experts from the Health Resources and Services Administration, the Indian Health Service, the Department of Veterans Affairs, Internet2, and the NIH National Library of Medicine, National Institute of Biomedical Imaging and Bioengineering, and National Center for Minority Health and Health Disparities. The conference brought together over 400 subject matter experts from government, academia, and industry to discuss a wide range of issues in telehealth research and development. Its primary outcome is a set of short papers reporting on recommendations from thematic breakout sessions and some overarching recommendations that can, taken together, stimulate and help guide further research through new multi-agency, interdisciplinary collaborations.

Post-publication sharing of data and tools.

Despite existing guidelines on access to data and bioresources, good practice is not widespread. A meeting of mouse researchers in Rome proposes ways to promote a culture of sharing.