From Bench to Bedside – Understanding the Academic Research Environment, the Challenges of Advancing Cancer Research and the Potential Power of Translational Management  
By Mark R. Kelley, Ph.D., Associate Director of Basic Science Research, IUSCC

Introduction
Research that translates from bench to bedside is the hallmark of National Cancer Institute-designated centers, such as the Indiana University Melvin and Bren Simon Cancer Center (IUSCC) in Indianapolis. However, even the NCI recognizes that inefficiencies inherent in academic research translation stall concept-to-care translation. In 2006, leadership at the IUSCC unveiled ITRAC© (Indiana University Simon Cancer Center Translational Research Acceleration Collaboration), a system of mapping successful translational pathways to achieve timely, as well as life saving and enhancing results for cancer patients. Early results suggest that it’s working.

Academic environments that foster interaction between laboratory and clinical researchers provide the greatest opportunities to translate basic science discoveries into clinically relevant research. However, current paradigms to facilitate academic movement of exciting and novel discovery-phase projects from the laboratory to animal testing and clinical trials have been cumbersome and unwieldy. It is the clumsiness of this process that has been scrutinized at the Indiana University Melvin and Bren Simon Cancer Center (IUSCC), and as a result, the IUSCC is taking the lead nationally in the implementation of a research management process that accelerates discovery and leads to translation.

Traditionally, the goal of pilot project funding within the IUSCC has been to help researchers with novel research ideas secure necessary data to apply for extramural funding. This seed funding typically ranged from $10,000 to $100,000. Some funding mandated investigator collaboration and/or that the investigator apply for extramural support once necessary data was acquired. The limitations of this system were that long-term success was not measured by new grants, new IP or new clinical studies. Clearly, a more efficient, accountable and outcome/metric-driven system was needed.

As a result, in mid 2005, an inter-disciplinary team of IUSCC members began to explore and assess innovative and potentially radical approaches to funding, managing and resourcing research activity. The aim of this team was to find a way to accelerate novel research leading to discoveries that could significantly reduce the human burden of cancer. Ultimately, what the team developed resulted in enhanced investigator collaboration, efficiencies in resource utilization and process transparency that promote translational success.

The IUSCC team began the process by asking fundamental questions. How can the IUSCC facilitate and augment the basic science research and improve the underlying science? How does the IUSCC create the internal capacity to recognize early on the most promising ideas, i.e., those with the greatest clinical and market potential? How are these ideas developed in a systematic way to continue their path to clinical trials efficiently? How does the university shift its culture from one of pure discovery to a more translational posture in order to become a powerful conduit of research that improves patient outcome?

Inquiry resulted in ITRAC© (Indiana University Simon Cancer Center Translational Research Acceleration Collaboration). ITRAC addresses the fundamentals of good science, translational opportunity, efficiencies in funding, technological and human resources, and provides momentum for success both individually and institutionally that drives a change in culture. In its essence, ITRAC leverages and applies the principles of portfolio and project management to the academic research environment. (The NCI is also pursuing a similar strategy and has formed a translational working group that parallels the ITRAC initiative, www.cancer.gov/trwg).

ITRAC is a flexible, integrated process charged with accelerating the translation of basic research into clinical application by forging collaborations and breaking down investigator silos. The ITRAC platform is designed around a milestone and incentive-based model that provides translational guidance and financial resources to move high potential research rapidly through research pathways that have traditionally been fraught with pitfalls and bottlenecks.

In return for a higher level of scientific scrutiny and accountability, individual researchers receive multiple benefits from utilization of ITRAC:

• Research mapped and managed by the ITRAC Translational Coordinator and researchers who are mentored by senior colleagues to better understand the pathway that leads to clinical impact
• Access to the Research Inventory & Collaboration Database (a searchable mechanism that provides an inventory of statewide human, biological and technological resources)
• Enhanced collaboration among IU Simon Cancer Center basic science and clinical researchers and with peers who have complementary expertise at other universities
• Acquisition of new technological resources based on current and projected usage data
• Streamlined translational initiatives that maintain momentum from bench to clinic and from clinic to bench
• Maps that enhance both external funding applications and opportunities for philanthropic support; and
• External advisors who collaborate in the review process to evaluate ‘real world’ usefulness of the project.

At ITRAC’s core is a protocol for resource management and allocation guided by IUSCC research leadership under the direction of Mark R. Kelley, Ph.D., Associate Director of Basic Science Research. Dr. Kelley, along with Translational Coordinator Mary Murray; Associate Clinical Director Christopher Sweeney, MBChB; and Associate Director of Strategic Partnerships James Klaunig, Ph.D., govern and facilitate the ITRAC initiative.

Research is prioritized for funding based on its progression through a series of ‘gates’ that allow for frequent review and re-evaluation. Research that meets a given gate requirement and continues to look promising will be well positioned to receive additional funding to advance toward the next gate. Research that does not meet the gate requirement is interrogated to build a better understanding of the research and its relationship to the cancer pathway – information that as it accumulates over time becomes an important asset for guiding future research. The initiative does not impede the funding or advancement of research activities and interests that ask the most fundamental of biological questions about cancer; rather, it is a mechanism to focus resources and accelerate research that is deemed to be more provocative, more likely to secure extramural funding, and more likely to have clear clinical potential.

Funding requests are conducted via three avenues and evaluated by the scientific committee:
1) Requests for Applications (RFAs) for a specific cancer, model or pathway
2) An advanced project that might be entering or already in a clinical trial that needs biological research support; and
3) Evaluation of the IUSCC research portfolio to determine, which projects need funding to accelerate and facilitate their progress to meet goals set forth in the IUSCC’s strategic plan

ITRAC is based on three premises – transparency, accountability and collaboration. Together, these qualities guide, augment and increase the quality of research relevant to the cancer-patient experience.

ITRAC ‘transparency’ allows all cancer center investigators to understand how funds are allocated, how the process works and how to access the process. Transparency also means that ‘pet’ projects – those that have previously been supported but not by means of a metric- or milestone-driven process – become obvious when ITRAC metrics are applied.

ITRAC ‘accountability’ is integrated into the pilot-project funding process. In order to secure IUSCC funding, projects must be mapped and gates established. Funding is allocated to move research from one gate to the next with the potential to reenter the process to secure additional funding if successful. This has been shown to accelerate promising research that extramural-funding cuts would otherwise have brought to a halt.

ITRAC collaboration is taking the form of expanded interactions of IUSCC investigators, not only on the Indiana University-Purdue University Indianapolis and Indiana University-Bloomington campuses, but also with investigators statewide at Notre Dame and Purdue universities.

1. Accelerating translational research
2. Increasing the quality and potential of the science
3. Leveraging institutional resources
4. Increasing the potential to attract funding

With the launch of ITRAC, the IUSCC committed funding to support a senior level project manager. An industry-based project manager was recruited and is currently implementing the ITRAC objectives, including mapping, portfolio management (assets of IUSCC), and finalizing the review/governance and criteria used to identify, review and prioritize research goals and opportunities and select specific projects to realize those goals.

From September 2006 through June 2007, internal funding was designated through the ITRAC Scientific Strategy group (ISSG) and over thirteen cancer projects have been funded with ten more under review. Over 43 additional cancer projects have been identified and mapped with more than 36 projects slated to be mapped in the immediate future. A strategy map is required for each proposal presentation, which includes a target date, the funding and other resources required to reach each successive milestone. The principle investigator (PI) presents the strategy map at each grant review and requests funding to answer the next critical question in the research process. As researchers achieve mapped benchmarks, they are encouraged to apply for additional project funding. Investigators receive immediate feedback from the committee on opportunities for collaboration and research enhancements. Follow-up at each milestone is accomplished through the ITRAC translational coordinator so that timelines, outcomes and funding utilization is communicated to the scientific review committee. All decisions are finalized by the senior members of the cancer center and approved by the cancer center director.

To date, the amount requested for pilot funding has totaled $703,541; yet, project goals have been satisfied with only $201,500 as necessary to achieve measurable milestones. Successful investigators are already returning for additional funding. Other projects have either not progressed or have not been successful and have been terminated by the investigator with new projects brought forward. Under the old system of pilot project granting, the IUSCC would have allocated $703,541 with limited success. With the new ITRAC system of resource allocation, more projects have been funded with less money and have achieved success in a shorter period of time. A bonus is that $500,000 remains to continue funding for projects that have demonstrated early milestone achievements.

• Also identified are 14 multi-institutional, multi-disciplinary collaborations – initiated by scientists, and after the mapping process identified the opportunity (e.g. technology transfer (IP) facilitation, funding sources identified, core capabilities/specimen libraries identified, etc.).
• Two shared resource facilities that have been receiving IUSCC financial support have been found to be under utilized and becoming less relevant for future cancer research. As a result cancer center funding that supports these facilities has decreased or been completely withdrawn. Financial resources are now being allocated to facilities with high cancer center-member usage.
• IUSCC investment is being made in six core capabilities or enhancements identified though ITRAC mapping that are currently needed or will be needed in the near future. One identified core has led to a new collaboration with the IUPUI Department of Chemistry.
• Finally, six connections with industry on behalf of a PI to promote research have been made.

In conclusion, the ITRAC initiative, while still early in its implementation, has already accelerated projects, identified needed resources, determined unused resources and has generated external funding. Investigators have been generally supportive of this benchmark-driven process, particularly once they have mapped their project(s) with translational coordinator and have been through the evaluation process.

Since implementation, this initiative has increased national visibility for the IUSCC and the Indiana life-sciences community. It is expected that this initiative will also dovetail with the central Indiana life-sciences initiative – BioCrossroads – to create more IU-initiated start-up companies and jobs that will decrease the ‘brain drain’ from the state (www.biocrossroads.com)

Short-term progress and success is encouraging, but the bar is set high for future results-driven metrics. The goal remains to accelerate the development of diagnostics, therapeutics and biomarkers that will have a positive impact on diagnosis, prognosis, treatment and quality of life for cancer patients. If successful, the academic research community will be able to answer the toughest questions of all – the ones asked by cancer patients.

Acknowledgements: Thanks to Mary Murray, IUSCC Translational Research Coordinator, for material included in this article. Additionally, thanks are due to Mary Maxwell, Development Director, IUSCC for reading, editing and offering comments on this article.