An outgrowth of the roadmap initiative is a new program that funds institutional Clinical and Translational Science Awards (CTSAs). Through this mechanism (http://grants.nih.gov/grants/guide/notice-files/NOT-RM-05-013.html), applicants may propose transformative efforts appropriate to their own institutions. The CTSAs will advance the assembly of institutional academic “homes” providing integrated intellectual and physical resources for the conduct of original clinical and translational science.

It is expected that the development of these environments will, over time, enhance the discipline, provide much-needed educational programs, contribute to the growth of well-structured and well-recognized career pathways, and provide a research environment that is more nimble, conducive to, and responsive to the demands of modern translational and clinical research. To allow institutions to build an innovative and integrated program, the NIH has asked applicants to consolidate General Clinical Research Centers (GCRCs), T32 and K12 programs, and other resources as appropriate. These resources may be augmented by substantial NIH Roadmap funding redirected from other initiatives and targeted to the CTSA program, with the National Center for Research Resources as the lead NIH entity. Recently, the NIH awarded a consortium of 12 institutions (http://www.ncrr.nih.gov/ncrrprog/roadmap/CTSA_9-2006.asp) the first funding through the CTSA program totaling $108 million the first year. The awards are for 5 years and the program itself will eventually replace the GCRCs.

One of the initial 12 CTSA recipients was the University of Pennsylvania (Penn) and its partner institutions, the Children's Hospital of Philadelphia (CHOP), the Wistar Institute and the University of the Sciences in Philadelphia . Their application included participation from the Schools of Medicine, Nursing, Dentistry, Education, Arts and Sciences, Veterinary, Engineering and Applied Sciences, the Annenberg School of Communications, and the Wharton Business School within Penn combined with colleagues from external partnerships into novel, interdisciplinary structures and programs. Penn and CHOP, together with their partner institutions include a large critical mass of senior faculty accomplished in the translation of a diverse array of therapeutic modalities - small molecules, proteins, genes, vaccines - into the clinical domain. Together they have a remarkable training record - more NIH supported training grants than any other institution, the largest medical science training program in the country and multiple junior faculty holding K awards. They also have two well established NIH funded GCRCs with potential to bridge the pediatric/adult interface. Finally, the group represents a single geographic campus facilitating the engagement of chemists, engineers, statisticians, nurses, veterinarians, dentists, pharmacists, policy makers and shapers and experts in commercialization with biomedical scientists, epidemiologists and physicians.

The Penn/CHOP transformational plan involves a commitment by the institutions involved to (a) collaborate and support the recruitments and programs in the field of clinical and translational research; (b) devote substantial space (wet and dry laboratories) to clinical and translational research; and (c) foster the trans-institutional expansion of the “academic home” of this enterprise - the Institute for Translational Medicine and Therapeutics (ITMAT) - to permit development of new centers, cores and interdisciplinary programs of research and education. An important goal for the Penn/CHOP plan is the development of focused strategic alliances with the FDA and the pharmaceutical and computing industries. Besides these alliances, the engagement of BioAdvance (http://www.bioadvance.com), a state funded entity charged with fostering the development of the life sciences in southeastern Pennsylvania has also been secured. BioAdvance will assist in providing resource for the access of trainees based with primary appointments in regional institutions to these educational instruments and will also support the development of and regionalization of access to bioinformatics platforms developed through the CTSA. The support of quantitative pharmacology practice will be provided by the KMAS (Kinetic Modeling and Simulation) Core which will (a) aid in the development of drug assays; (b) promote and assist in the performance of tracer kinetic studies; (c) develop novel approaches to kinetic data analysis; (d) provide PK, PK/PD, and tracer kinetic modeling; and (e) develop educational modules in pharmacokinetics and tracer kinetics to populate the educational initiatives pursued within the CTSA.

central mission of ITMAT will be education. The deficiency of human capital in translational research, particularly with respect to the development and evaluation of new medicines is well appreciated and pervasive in industry, academia and the regulatory community. The ITMAT has proposed the name “Translational Medicine and Therapeutics” to embrace the projection of basic disciplines into the clinical domain with the objective of developing novel therapeutics. Such individuals would be trained in the development and projection of mechanism-based biomarkers from cellular and model systems to guide rational dose selection. Furthermore, they would be trained to apply the emerging use and bioinformatic analysis of output from technologies, such as proteomics, metabolomics and genomics, to select between diverse molecules directed at a singular target. While the KMAS core will provide functional support of quantitative pharmacology activities, a Pharmacometric Training Unit will provide educational and training resources in addition to previously created programs in translational medicine. Initially, a module on tracer kinetics, pharmacokinetics, and compartmental and pharmacometric modeling will be offered as a core requirement in a Translational Therapeutics track and electively as a stand alone course or a component in other degree courses administered via ITMAT in support of the CTSA. PhRMA and FDA staff will participate, both as faculty participants and as rotation site for CTSA students. BioAdvance will facilitate regionalization of access to this program.

Clinical and Translational Science (CTSA)