Imaging Integration and Implementation (I2) Team
Business Plan: Executive Summary
- Introduction
- Business Opportunity
- Vertical Product Lines
- Horizontal Product Lines
- Project Management
- Conclusion
Introduction
Imaging is a form of in vivo assay. It provides spatially localized information about some property of matter. Traditionally, clinical imaging has displayed matter's structural or anatomic properties. However, it is now increasingly possible for imaging to depict chemical properties. This makes imaging invaluable in the new era of molecular medicine. As cancer is redefined in terms of its molecular signature, in vivo imaging can display molecular information that will: (1) indicate what molecular phenotype is present; (2) direct the localization of therapy; and (3) signify whether the cancer is responding to therapy.
NCI is a recognized leader in stimulating the field of molecular imaging as well as fueling advances in small-animal and clinical imaging. NCI currently funds about $200M in imaging-related grants, cooperative agreements and contracts covering a wide variety of basic and translational research. However, this funding is dispersed over a wide variety of research topics, technologies, and strategies. This diverse portfolio is both a strength and a weakness. The strength, of course, is that discoveries and innovations are not predictable, and a variety of approaches must be supported. The weakness is that a cohesive development process will not necessarily emerge from the multiple-independent-laboratory approach, and delivery of mature applications or infrastructure may be considerably delayed. A managed, directed business approach toward certain aspects of research and development can provide selected, specified deliverables in a more predictable way. I2 Imaging focuses on a few such areas of imaging research that: (a) have a high priority for helping NCI attain its 2015 Challenge Goal; and (b) can be expected to have a realistic, predictable, and manageable timeline.
Mission: I2 Imaging delivers a suite of Product Lines that will employ imaging to:
- Better understand the biology of cancer and its microenvironment.
- Contribute to the preemption and early detection of cancer and precancer.
- Improve efficiency in the development of cancer therapies and provide early evidence of therapeutic effectiveness during their development and dissemination.
- Improving the imaging informatics infrastructure.
- Accelerating the delivery of new imaging agents, devices, systems, and platforms for research, preclinical, and clinical use.
- Supporting the development and delivery of image-guided interventional treatments.
To accomplish its Vision, I2 Imaging develops products that enhance in vivo imaging's ability to display molecular information that will: (1) indicate what molecular phenotype is present; (2) direct the localization of therapy; and (3) indicate whether the cancer is responding to therapy. Given that it is not appropriate for government to compete directly with private business, I2 Imaging focuses on products that the private sector will probably not develop and that will not likely be funded through traditional investigator-initiated grant mechanisms. This business plan is not intended to represent a comprehensive strategic plan for all imaging activities across all organizational units within NCI. Rather, it is intended to identify specific projects where targeted investment will lead to measurable outcomes that will in turn contribute in a fundamental way to attaining the NCI 2015 Goal. Investment in a variety of investigator-initiated research activities will continue to be essential and will continue to be supported by the usual NCI and NIH mechanisms. I2 Imaging pursues projects and activities that are either not being done or are not being done in a coordinated, managed way directed toward specified goals. In particular, this means that I2 Imaging focuses on developing pathways and processes for development of imaging as a biomarker for therapy development; pathways and processes that lead to indication-specific FDA approval of image-guided ablative therapies; and the infrastructure necessary to accomplish those tasks, such as development of software, imaging agents, and image archives, as well as informatics infrastructure.
Business Opportunity
Imaging will speed progress toward the NCI 2015 Challenge Goal by improving cancer management (including detection, diagnosis, treatment delivery, and surveillance) and preemption (including early detection and monitoring of preneoplasia) and by increasing our understanding of cancer biology (as an essential laboratory methodology).
Imaging can be a primary or important secondary endpoint in therapy trials. Therefore, imaging in cancer clinical trials needs to be performed in standardized ways, and the images need to be transmitted to central archives to ensure validity of the data and create resources for subsequent research. The infrastructure, procedures, and culture needed to accomplish this will not occur from the funding of individual research grants. This is technologically achievable today, but resources need to be deployed in accordance with an organized plan to make this happen. I2 Imaging sees a clear opportunity to develop and provide these products.
Furthermore, there is a need to develop targeted imaging agents that are tied to specific targeted therapeutic agents such that the imaging agent can identify patients with the appropriate molecular phenotype for the targeted drug. Currently the development of such targeted imaging agents is out of phase with, and lags behind, the development of therapeutic agents. I2 Imaging seeks ways to bring these two developmental activities into phase with one another.
Preemption of cancer is an important priority for NCI and a major challenge for in vivo imaging. Using imaging to identify the structural or biochemical signs of small, preneoplastic lesions requires chemical and or spatial resolution that is beyond the current state of the art for clinical imaging. However, there are many successful examples in the research laboratories of industry, where resources were targeted to solve such specified problems. I2 Imaging sees an opportunity to identify one or more specific problems and address them using an organized, managed approach.
In vivo imaging is now an indispensable laboratory tool, both at the cellular level and the small-animal level. Exciting progress is being made in individual laboratories, aligned with the priorities and interests of the principal investigators in those laboratories. There is a need to focus some of those developmental efforts at priorities established by the NCI in terms of understanding the cellular communications between cancer cells and their surroundings. In vivo imaging of molecular events in living cells will be an essential component in elucidating the systems biology of cancer. I2 Imaging sees a vital opportunity to define one or more challenges for imaging of the microenvironment and design strategies for overcoming them.
There is an opportunity for I2 Imaging to develop a strategic alliance with I2 Informatics to develop an Imaging Workspace within the Cancer Bioinformatics Grid (caBIG) project http://cabig.nci.nih.gov/workspaces/Imaging. The I2 Imaging Board of Directors will include at least one member from the NCI Center for Bioinformatics (NCICB) to ensure coordination between I2 Imaging and I2 Informatics http://imaging.nci.nih.gov.
There is a similar opportunity for I2 Imaging to develop a strategic alliance with the I2 Team for Lung Cancer to focus on the development of imaging tools for the early detection of lung cancer and the validation of imaging methods as biomarkers for the development of lung cancer therapies. The I2 Imaging Board of Directors will include at least one member from the I2 Team for Lung Cancer to ensure coordination between I2 Imaging and the I2 Team for Lung Cancer.
There is a similar opportunity for I2 Imaging to develop a strategic partnership with the NCI Nanotechnology Alliance for the development of nanoparticle-based imaging agents. The I2 Imaging Board of Directors will include at least one member from the NCI Office of Technology and Industrial Relations (OTIR) to ensure coordination between I2 Imaging and the NCI Nanotechnology Alliance.
To take advantage of these opportunities, I2 Imaging has chosen to invest in eight Product Lines. The first four Product Lines can be considered vertical Product Lines, each somewhat independent of the others. The last four Product Lines are horizontally integrated Product Lines, the products of which could support more than one of the first four vertical Product Lines.
Vertical Product Lines
Imaging for Cancer Prevention and Preemption
Vision: By 2015, imaging will play a significant role in the prevention and preemption of cancer.
Goal: Use imaging to define the cancer risk and precancer burden in individuals and aid, augment, and monitor therapies for treatment and prevention of cancer and precancer.
Imaging Tools for Early Therapy Development
Vision: By 2015, imaging will play a significant role in making “go/no-go” decisions for early therapy development.
Goal: Use imaging methods to decrease the time and cost involved in early oncologic drug development.
Imaging Tools for Late Therapy Development
Vision: By 2015, imaging tests or methods will serve as surrogate markers of therapy response for late-phase clinical trials.
Goals: Develop a pathway and perform demonstration projects to test that pathway to qualify anatomic, dynamic, and molecular imaging methods as reliable surrogate markers for therapy response.
Development, Validation, and Dissemination of Oncologic Image-Guided Intervention (IGI)
Vision: By 2015, image-guided interventions (IGIs) will play a major role in the prevention and preemption of cancer.
Goals: Develop the infrastructure, procedures, and processes necessary to obtain application-specific FDA approval of IGI devices and conduct demonstration projects to test this pathway.
Horizontal Product Lines
Imaging to Promote the Understanding of Cancer Biology and the Cancer Microenvironment
Vision: By 2015, high-resolution in vivo imaging in molecular and cellular biology will be instrumental in defining fundamental genetic and biological processes involved in tumorigenesis, metastasis and complex interdependencies between tumor cells and their microenvironment.
Goal: Make widely available the tools necessary to noninvasively and quantitatively interrogate the cancer cell, its tumor microenvironment, and its response to therapy.
Development, Validation, and Dissemination of Imaging Agents for Oncology
Vision: By 2015, high impact imaging agents (including nanoconstructs) will be a pivotal resource for oncology research and clinical care.
Goal: Make widely available a portfolio of imaging probes that will be critical to elucidating tumor biology, accelerating drug development, optimizing detection and directing therapy for cancer.
Development, Validation, and Dissemination of Imaging Technology for Oncology
Vision: By 2015, imaging technology will play a significant role in reducing suffering and death due to cancer.
Goal: Provide publicly accessible clinical trial image databases linked to clinical outcomes as resources for the development of quantitative image tools applicable to cancer.
Imaging Informatics
Vision: By 2015, the NCI imaging informatics infrastructure will be an indispensable resource for oncology research and clinical care.
Goal: Create an informatics infrastructure so pervasive and useful that its existence will be taken for granted by those who use it and its existence will be taken for granted by those who use it.
Project Management
I2 Imaging as an endeavor requires the implementation of an organizational structure that supports the transformational business strategies presented in this proposal to achieve our desired business model. However, we also propose to integrate the imaging components of many ongoing activities into the overall I2 Imaging business plan. Therefore, the organizational structure must respect and leverage already established and functional organizational structure. In fact, these seemingly contradictory objectives can be easily met by employing a standard organizational model from the for-profit sector with slight modification.
I2 Imaging is led by the I2 Imaging Board of Directors, which reports to the NCI Executive Committee. Daniel Sullivan, head of the Cancer Imaging Program in DCTD, chairs the I2 Imaging Board. Members of the I2 Imaging Board of Directors are senior staff members from the various organizational units within NCI that have significant interest or programs in imaging and include NCI Deputy Director Mark Clanton as liaison to the Director, NCI, and Cherie Nichols, head of the NCI Office of Science Planning and Assessment (OSPA). The current Board has authored and supports this proposal and has continued interest in its implementation and success. However, the members of the Board cannot and should not have day-to-day managerial responsibility. The Board members' knowledge base, interest, and investment in the endeavor's success make them ideally suited to serve on the I2 Imaging Board of Directors.
The I2 Imaging Board of Directors will not have direct day-to-day managerial responsibilities but, instead, will provide oversight, general direction, and, probably most importantly, the high-level buy-in to facilitate success. The current NCI structure is not optimal in all cases to promote collaboration, joint project ownership, and budgetary consolidation across Divisions and programs. Involving the top-level "owners" within the Board should overcome such largely artificial boundaries. It is also strongly requested that there be representation from the highest levels of the NCI so that real-time decisions that might be viewed as transformational can be made and implemented without unnecessary delay. Since I2 Imaging will be held to its proposed business plan, every effort should be made to create an organizational structure that removes barriers and facilitates desired outcomes. Obviously, if commitment to contemporary corporate business practices utilized in well-run for-profit entities (although perhaps novel within the Federal Government) is lacking, it will be impossible to make these commitments to timely delivery of milestones and return on investment (ROI). Individual members of the Board (referred to as "Board Liaisons") have been assigned direct oversight for specific Product Lines but, as importantly, will have conjoint oversight for the I2 Imaging global effort.
I2 Imaging will also be staffed by a Management Team, separate from the Board of Directors except for the Management Team Leader, who will also serve as the Chair of the Board, as is frequently the case in the organizational structure of for-profit and not-for-profit corporations (i.e., the Chief Executive Officer as Chairman of the Board). The remainder of the Management Team will each have direct-line responsibility for one of the proposed Product Lines, including budgetary and outcomes accountability. Members of the Cancer Imaging Program (CIP) staff will serve as the management team under the continued leadership of Dr. Sullivan.
Members of the Management Team under the direction of the Board Chair and the Board have organized Product Line-specific work groups. Each work group has created detailed action plans to implement each of the objectives within the specific Product Line. The Product Line-specific work groups are composed of representatives from all pertinent parties within the Institute as mutually agreed upon by the Board Liaison and the Product Line Manager, and as approved by the full Board. The work groups are sized so as to be as inclusive as necessary while retaining the ability to be functional.
Conclusion
I2 Imaging's products deliver important outcomes and capacities to our targeted end users (researchers, providers of clinical care, patients, patient families, and the American public).
Specific deliverables to our customers will include:
- Infrastructure and standard operating procedures for centralized interpretations of images so that imaging can be used as an important endpoint in drug trials.
- Databases of images and associated clinical data as research resources for the development of algorithms for computer-assisted diagnosis (CAD).
- Validated functional imaging tests and novel targeted imaging agents to use as biomarkers in clinical therapy trials and, eventually, to support clinical medical decision making.
- Validated minimally invasive or noninvasive image-guided ablative therapies for localized tumors.
The Mission, Vision, and desired outcomes of I2 Imaging are worthwhile because they will permit imaging to be used as primary and secondary endpoints in clinical trials of therapies, thereby reducing overall trial duration and decreasing the number of patients needed for trials. Harnessing the images and clinical data from clinical trials in central repositories will enable secondary analyses and research to be performed, such as those on computer-assisted detection or diagnosis (CAD) algorithms. Efforts to make available validated imaging tools and image-guided interventions through support of development, optimization, and clinical trials for validation will provide direct benefits to cancer patients and their families.
If these efforts are not undertaken, progress in developing new cancer therapies will be fragmented and prolonged. Opportunities to develop imaging as a biomarker, develop resources from images and data obtained in clinical trials, and develop better tools for understanding cancer biology will be lost.
