A full spectrum of translational science
Basic science discoveries feed the pipeline for translational and clinical research that seeks to move discoveries into practice and policy to improve health. Establishing the efficacy of a new drug, biologic, device, diagnostic or preventative intervention through clinical research in controlled experimental settings creates preliminary evidence for application to clinical practice. While the establishment of safety and efficacy is requisite to availability of new therapies, proof of real-world safety and effectiveness is equally vital to actually affect health. We believe that CTSAs must support all of these stages if we are to systematically improve health; therefore, CTSAs, in the aggregate, cover the entire spectrum of translational science. Importantly, the process by which translational science occurs requires an institutional framework entailing familiarity with all stages, and as such, the `science of translation' has become a fundamental focus and principle of the CTSAs. Wisely, in authorizing NCATS, Congress encouraged the new Center “study steps in the therapeutics development and implementation process…to identify bottlenecks…that are amenable to re-engineering, and develop new technologies and innovative methods for streamlining the process.”5
The large number of C&T studies supported or conducted under the auspices of the CTSA programs provides a platform for process analyses that, working with operations experts, address this deficiency and holds promise for ways to reengineer processes6
A disease-agnostic approach to providing infrastructure
As scientists we can understand the notion that infrastructure is not always the most alluring topic. But as CTSA Principal Investigators and institutional leaders, we have begun to see the immense importance in the creation of a resource/program/service that: 1) works across disease areas, 2) does not have to be recreated, and 3) fuels scientific innovation by its very existence. The nature of our operations in creating broad, reusable infrastructure is one of the most prominent symbols of what we do. There is a proxy for measuring the extent to which we perform well: grant funding obtained from NIH's categorical Institutes and Centers (I/Cs). CTSA support systems (some described here) positively impacts the diverse research funded by the NIH Institutes, Centers, and Offices. Indeed, in the most recently reported project period, the CTSA program supported the research activities of 5,886 unique NIH grants (). Moreover, the support provided often reduces costs for the services offered, extending the purchase power of the NIH funding. CTSA support is supplemented by considerable institutional matching. That Deans and CEO's are willing to co-invest (substantially, in most cases) in this infrastructure is yet additional evidence of the perceived benefits of the CTSA model.
Federal grants that benefited from the CTSA grant resources for investigators whose research was aided by the resources of the CTSA (as reported in site specific annual progress reports, 2010):
Supporting investigators in early-stage, hypothesis-driven pilot studies
Allocation of pilot funds is an imperative function of the CTSAs to jumpstart innovative science. All sites support pilot and collaborative studies that allow clinical and translational trainees or researchers to generate preliminary data for submission of grant applications, and/or are intended to develop innovative methods and technologies and new collaborations. Local CTSA pilot support of health related research provides for rapid funding that is typically not available through other sources and is essential to investigators who need to generate preliminary data. These programs are designed to be flexible and responsive to changing opportunities in the field by providing unique resources and fostering new investigative talent in different disease domains. CTSA sites follow accepted standards of rigorous scientific review. Scientific review of the proposed health-related research is handled by faculty who are knowledgeable in the various disciplines and methodologies related to the scientific areas of the applicants. This distributed model for funding pilot studies using CTSA and matching institutional support provides small-scale and early-stage funding. Approximately 2,000 pilot studies were conducted across CTSAs in the last reporting year (), greatly enhancing the resultant quality of preliminary data and simultaneously de-risking subsequent submissions to NIH and other federal funding agencies. It also represents a flexible infrastructure for locally offered RFAs that can reflect NIH priorities.
Pilot programs are supported at every CTSA; these programs stimulate essential, small-scale scientific investigation.
The CTSA consortium has served an active role in not only providing research-focused support for regulatory compliance and management, but in greatly streamlining processes at the institutional level. Spurred by nationwide comparative studies of protocol processing times, many CTSA sites have measurably reduced the length of time for IRB protocol review and approval, as well as contract negotiations and final agreements. Development of IRB consortia has emerged, providing multiple-site, single IRB research networks. Many CTSA sites are also implementing an OHRP-approved, collaborative IRB review model supported by an electronic sharing resource. Also, consistent with the NCATS mission of advancing the underpinning methods of translational science, CTSAs are contributing novel approaches to clinical trial design (such as N-of- 1 and innovative adaptive designs), conduct, and analysis that interface with the regulatory requirements in ways that will enhance translation of new treatments into use. In addition, every CTSA provides research participant advocacy functions which work with investigators, trainees, and research teams to promote and facilitate the safe and ethical conduct of human research.
Recruitment and retention has become a predominant concern due to recognition that failure to enroll any subject is not rare in clinical studies, and failure to recruit the target number of subjects is common7
. As one example of a tool to help in recruiting volunteers, the CTSA-supported ResearchMatch is a disease-neutral, institution-neutral, web-based research matching service. Without significant publicity and no advertising, 20,000 registrants have volunteered (and simultaneously learned more about how they can help advance science as participants) and ResearchMatch already serves ~1,000 researchers regardless of disease focus8
. CTSAs are also starting to use an i2b2 or other Electronic Medical Record (EMR)-based systems to establish protocol cohort development at given sites to document the adequacy of patient populations (e.g. rapidly quantify numbers of subjects with specific diseases). At several CTSA sites, these and other strategies have resulted in an increase from 60% to 125% in the target subject accrual rate for clinical trials9