Spectrum Of Translational Research Research Articles

From the Editors’ Desk: Why NCATS Should Read this Issue of JGIM

From the Editors’ Desk: Why NCATS Should Read this Issue of JGIM

Merck's reCalibration

Merck is investing up to $90 million over the next seven years to fund the California Institute for Biomedical Research. The pharma is hoping the wide spectrum of translational research to be covered by the institute will yield first access to drugs against new targets that might not yet be on the company's radar.

White Paper on CTSA Consortium Role in Facilitating Comparative Effectiveness Research

Background Appreciating the need to better translate biomedical research into improved clinical care and health, the NIH Roadmap was initiated in 2003 to focus on this by strengthening NIH’s central role in clinical research and clinical research training. As part of the needed re-engineering, in 2006 NIH began the CTSA program. At this writing (Summer 2009), there are 39 CTSAs at leading universities across the United States, each having a clinical research graduate program and extensive resources for promoting clinical and translational research. Each of these, and the CTSA Consortium as a whole, are committed to transforming clinical and translational research to maximize impact on health. The CTSAs bring to this challenge an array of capacities, extensive research infrastructure, formal training and career development programs, community engagement of the public and of clinical practice communities, and informatics related to research and clinical practice. Various CTSAs have different areas of emphasis, including along the spectrum of translational research from bench to patient bedside (the first translational step, “T1”), from the bedside to general use in clinical practice (“T2”), and from clinical practice to public benefit and policy (“T3”). This broad array of activities has allowed the national consortium to be responsive to needs all along this path of translation of biomedical research into practice and public benefit. Although the activities of CER can be seen as primarily involving T2 and T3 research, they also can be seen as focusing on the optimal translation of T1 research into effective treatment, and thus the very epitome of work in which CTSAs should be deeply involved. This appreciation was reinforced by CER’s selection as a key Strategic Goal focus of the CTSA Consortium. In this context, the CER Strategic Goal of the CTSA Consortium is to promote the translation of the results of clinical and translational research into practice and public policy. In service of this, in two sections below, we review the span of CER resources across the CTSA Consortium and propose potential roles for CTSAs in supporting CER. As a point of reference for this White Paper, below are two important definitions of CER from reports released at the end of June 2009, from the IOM and from the FCC-CER: Definition from the IOM Report on Priorities for CER The generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. The purpose of CER is to assist patients, clinicians, purchasers, and policy makers, and the public to make informed decisions that will improve healthcare at both the individual and population levels.

What Can Be Done to Protect the Translational Investigator?

The Association for Patient-Oriented Research (APOR) arose from concerns expressed beginning in the late 1970s about a growing shortage of investigators interested and well trained in conducting research on human subjects. Educational debt, difficulties in securing grant funding, and greater financial rewards in clinical practice continue to discourage young practitioners from pursuing careers in clinical research. Academic medical centers have seen their margins from clinical earnings decline and have asked potential clinician-investigators to contribute to the bottom line by seeing more patients. There was also an assumption, mostly unspoken, that basic research should be the focus of support and training, and that self-evident clinical and public health applications of basic research findings would be developed without much support from government or academic institutions. But the translation of basic research knowledge to the clinic and community has proven to be challenging and complex, and the rate by which the pharmaceutical industry has been developing significant new drugs is disappointing. An especially endangered species is the clinical investigator who asks questions at the bedside, and may then pursue answers initially in the laboratory and animal models before returning to the patient with a scientifically meaningful and ethical research protocol. This bidirectional aspect has been recognized as an essential and exciting aspect of patient-oriented research for many years, as exemplified by the comments of John Oates in 1982 (Figure 1). The career development of effective investigators who are comfortable both at the bedside and in the laboratory requires many years of mentoring and experience as well as stable research funding and institutional support. Integral role of patient-oriented clinical investigation both in the discovery of new knowledge and development of new therapies (from Oates JA. Presidential address: Clinical investigation: a pathway to discovery. Trans Assoc Am Physicians. 1982; 95: lxxviii-xc). Since the 1950s, the National Institutes of Health (NIH) has provided basic infrastructure for patient-oriented research in academic medical centers through the General Clinical Research Center (GCRC) program. GCRCs were also important for training patient-oriented investigators. In the 1990s, the NIH initiated K30 grants, which supported development of curricula for clinical research education, and individual K grants for trainees (NCRR K12), young investigators (K23, K08, etc.), and mentors (K24). The NIH Roadmap proposed by former NIH Director Elias Zerhouni, MD, emphasized clinical research and culminated in the Institutional Clinical and Translational Science Awards (ICTSAs). APOR supports the ICTSA program, which aims to expand support across the broad spectrum of translational research—from bench to bedside and the community—and for training at multiple levels. Unfortunately, this comprehensive program is being implemented at a time when NIH funding is limited. There are no progress reports yet on ICTSAs, but concerns have been expressed that at some institutions infrastructure for patient-oriented research has been downsized and that support has shifted to more basic research in the translational spectrum. If so, this will impede development of patient-oriented researchers. Current plans are for fewer ICTSAs than the number of previous GCRCs, which may mean that students and junior faculty at many academic health centers will have little exposure to hypothesis-driven, investigator-initiated clinical research. Clinical research at such institutions may be visible only as clinical trials sponsored by the pharma. While partnering with pharma is a key component of the NIH Roadmap, academic centers must also provide an environment favorable to patient-oriented research that investigators pursue based on hypotheses generated at the bedside. APOR will continue to promote patient-oriented research in a rapidly changing healthcare and clinical research environment. Because patient-oriented research represents a partnership between all practitioners and patients affected by disease, APOR welcomes all who are interested in CTS research to join in this effort. APOR is partnering with other organizations with complementary goals, such as the Society for Clinical and Translational Science (SCTS) and the Association for Clinical Research Training (ACRT), in planning an annual spring meeting that will benefit members of all these organizations. APOR and SCTS are also partners in supporting CTS. APOR will continue to provide further information about its activities in future issues of this journal, as well as in our newsletter (http://www.apor.org).

Reengineering Clinical Research with Informatics

The future success of the translational research spectrum depends on the clinical research enterprise's ability to break through the barriers that constrain its productivity. As more basic science discoveries emerge,...

Policy analysis: an essential research tool for the introduction of vaccines in developing countries.

To address the unacceptable levels of disease in developing countries and the lack of vaccines to address infectious diseases, the public sector has been expanding its funding for, and involvement in, vaccine research and development. The public sector is becoming a full participant in the spectrum of translational research taking candidates from the laboratory to use in national immunization programmes. As these programmes and the continuing work of the private sector achieve success, an extensive analysis of policy will be needed to support the introduction of vaccines. Based on the early experience with the introduction of hepatitis B vaccine in several developing countries, there is a defined framework for the introduction of vaccines. This framework lays out five essential overlapping and complementary elements of introduction of vaccines in developing countries. Each element requires a clear understanding of policy-related issues. There is a pressing need to include and expand policy analysis on a wide range of topics to ensure that the poor in developing countries can have access to the fruits of modern biotechnology.