President's Cancer Panel Meeting- The Future of Cancer Research: Accelerating Scientific Innovation, Transcript of Proce by National Cancer Institute . - HTML preview

OPENING REMARKS—DR. LaSALLE D. LEFFALL, JR.

On behalf of the Panel, Dr. Leffall welcomed invited participants and the public to the meeting. He introduced Panel members, provided a brief overview of the history and purpose of the Panel, and described the aims of the current series of meetings.

Dr. Kripke reported that the Panel held Working Group meetings on February 19, June 30, and September 8, 2010, to discuss policy, research, and program recommendations for the 2009-2010 Annual Report to the President. Dr. Kripke’s motion to accept all of the recommendations of the Working Group was unanimously passed.

PANEL I

DR. JAMES DOROSHOW:

CHANGING THE NCI’S CLINICAL TRIALS SYSTEM TO MEET THE NEEDS OF THE  21ST  CENTURY: FOCUS ON MOLECULAR CHARACTERIZATION OF TUMORS FOR  PATIENTS ENTERED ON CLINICAL STUDIES

Background

Dr. James H. Doroshow has been the Director of the NCI Division of Cancer Treatment and Diagnosis since 2004. From 1983 to 2004, Dr. Doroshow was the Chairman of the City of Hope Comprehensive Cancer Center Department of Medical Oncology and Therapeutics Research. From the time of his first research grant in 1980, Dr. Doroshow was continuously funded by NCI until he moved to NIH in 2004. He is the author of over 300 full-length publications in the areas of anthracycline antibiotic molecular pharmacology, the role of oxidant stress in tumor cell signal transduction, and novel therapeutic approaches to solid tumors. Dr. Doroshow served from 1990–92 as Chairman of the NIH Experimental Therapeutics II Study Section, from 1995–2001 as a member of the Subspecialty Board on Medical Oncology of the American Board of Internal Medicine, from 1999–2000 as Chairman of NCI’s Scientific Review Group A-Cancer Centers, and from 2004–2007 as a member of U.S. Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee. From 2004–2005, Dr. Doroshow chaired NCI’s Clinical Trials Working Group, which developed a comprehensive set of initiatives to restructure the national cancer clinical trials enterprise.

Key Points

• One of the most important issues currently facing NCI is the need to improve and update its clinical trials system to meet the requirements of the 21st century. Necessary to this endeavor is the collection of biospecimens for research and molecular characterization patients. Facilitation of these activities will be essential to NCI’s quest to bring new, effective cancer-fighting treatments to patients.
• The development of predictive therapeutic markers encompasses a broad range of activities that begin in the early stages of drug development. An assessment of NCI’s research portfolio reveals a large amount of funding devoted to predictive marker identification, to early-phase feasibility testing, and to the detection of biomarkers. However, the resources needed to move past early discovery to the development phase are lacking.
• This resource need, along with the recent availability of stimulus funds, has led to the creation of the Clinical Assay Development Program (CADP). This program provides intramural and extramural resources to facilitate the efficient development of diagnostic tests needed to speed the evaluation of molecularly targeted therapies. This program also serves to overcome the inefficiencies and lack of support for therapeutic and predictive biomarker development. NCI is creating a rigorous development process that will allow for the use of biomarkers in stratification, treatment assignment, and eligibility assessment in the context of clinical trials. Resources will be provided to optimize analytical performance and establish the clinical validity of biomarker studies.
• The Clinical Assay Development Program (CADP) comprises four parts. The first is the Clinical Assay Development Network (CADN), which is a group of Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories in academia and industry with the purpose of facilitating the transition of biomarkers into the clinic in a manner that brings them closer to FDA certification.
• A Patient Characterization Center, the biomarker discovery piece, is being developed on the NCI— Frederick campus. This center will be a model for the development of personalized, highly prescriptive cancer care. This care will be based on traditional epidemiological and risk-factor analysis combined with molecular and pharmacogenomic characterization of patients and their tumors. Ultimately, the Center will have the capacity to perform complete genomic characterization of patient specimens (normal and tumor). All of this information will be publicly available pending patient consent.
• The Clinical Assay Development Centers (CADC) will work in concert with the CADN to create a process to efficiently develop diagnostic tools that will address clinical needs, including but not limited to tools that can assess prognosis, inform patient selection for testing of molecularly targeted agents, and predict response to therapy. Initially, the emphasis will be on evaluating the performance characteristics of assays proposed for use in clinical trials. The CADC and CADN will provide the resources to optimize and validate assays. Project teams that include pathologists, statisticians, and experts in assay development will be formed to design the studies needed to carry the assay development process to completion.
• CADP will utilize an outside peer-review process by a special emphasis panel of individuals from industry and academia. The most highly rated projects will be evaluated for their feasibility by various internal committees and then overseen by a group of project management teams in conjunction with NCI staff and the principal investigators.
• The fourth component of the CADP is the Specimen Retrieval System. A contract has been established with Northern California Kaiser to provide these services.
• To date, eight CLIA-certified laboratories have signed contracts to participate in CADN. About half of the staff for the Patient Characterization Center and CADC in Frederick have been hired and will be operational by January 1, 2011. It is anticipated that the first application for utilization of the CADP will be received in the first quarter of 2011.

DR. LISA RICHARDSON:

ADVANCING CANCER PREVENTION AND CONTROL THROUGH COORDINATION  AND DISSEMINATION

Background

Dr. Lisa C. Richardson is the Associate Director for Science in the Centers for Disease Control and Prevention Division of Cancer Prevention and Control (CDC/DCPC). Her research focuses on access to cancer care, systems of care, health-related quality of life during cancer treatment, health disparities and racial discrimination, and breast cancer treatment patterns of care. Dr. Richardson oversees the research and scientific content of the DCPC products. The Division administers the only organized screening program for low-income uninsured women in the United States (National Breast and Cervical Cancer and Early Detection Program). The Division also administers the National Program of Cancer Registries. This program, in collaboration with the NCI Surveillance, Epidemiology and End Results (SEER) registries, covers 98 percent of the U.S. population for cancer incidence.

Key Points

• The CDC Division of Cancer Prevention and Control provides essential public health services, including monitoring health status; informing, educating, and empowering the public; mobilizing community partnerships; developing policies and plans; linking people to needed services and assuring care; and evaluating health services and conducting research. CDC views research as one of its essential services and may mandate its programs to conduct more research in the future.
• DCPC addresses cross-cutting issues across the cancer continuum, from prevention to diagnosis to survivorship. Some of these issues include communications, surveillance (one of the CDC’s core functions), genomics, and policy change. CDC provides health services in the context of the cancer continuum, implementing interventions where the evidence is strongest. For example, evidence for effective intervention for breast cancer may be strongest in the area of early detection, so that is where CDC would devote most of its efforts to make an impact.
• DCPC’s largest health intervention initiative is the National Breast and Cervical Cancer Early Detection Program. This program is for under-and uninsured women who would like to be screened for breast and cervical cancer. To date, about 4 million women have been screened.
• DCPC’s second-largest initiative is the National Program of Cancer Registries, which collects data on the occurrence of cancer; the type, extent, and location of the cancer; and the type of initial treatment. This program supports 45 state cancer registries, which are complementary to NCI’s SEER Program.
• The third-largest DCPC health initiative is the National Comprehensive Cancer Control Program, which currently supports 50 states, the District of Columbia, 7 tribal groups, and 7 U.S.-associated Pacific Islands/territories to establish coalitions, assess the burden of cancer, determine priorities, and develop and implement cancer plans.
• The Prevention Research Centers is a network of public health agencies, community members, and 40 public health schools that conducts applied research in disease prevention and control. Within these Centers, the Cancer Prevention and Control Network was established to provide expertise for research that meets the Guide to Community Preventive Services standards. The Guide is a free resource that offers program and policy suggestions to improve health and prevent disease in the community.
• CDC cancer surveillance data have been used to inform the Agency for Healthcare Research and Quality’s (AHRQ) National Healthcare Quality and Disparities reports and state snapshots, which provide state-specific health care quality information. CDC also provided data for Healthy People 2020, which should be released in December 2010.
• CDC’s foremost cancer priorities revolve around primary and secondary prevention. Primary prevention involves implementing interventions known to reduce the risk of cancer forming— vaccination (e.g., HPV, HBV), smoking cessation, obesity prevention, and increasing physical activity. Secondary prevention is the early detection of disease, which encompasses the entire cancer care spectrum, from getting screened to being diagnosed and receiving therapy and survivorship care.
• As of 2006, there were nearly 12 million cancer survivors in the United States, which is 4 to 5 percent of the total population. Yet, little research has been conducted on patients’ lived experience with cancer. Elucidating the cancer patient’s experience and improving the quality of life of cancer  survivors is one of CDC’s top priorities. Unfortunately, funding has not yet been provided to truly make an impact in this area.
• The current paradigm for translating research from “bench” to “beside” needs to change. Effective health interventions must be informed by research. However, some public health officials estimate it can take as long as 30 years to translate research into practice. One possible avenue to efficiently disseminate research findings to the public is to utilize the existing public health infrastructure. For example, CDC has cancer control programs in every state, which could serve as a vehicle to disseminate information to the public.
• The CDC National Center for Chronic Disease Prevention has developed its own framework for translating research into practice—the Health Promotion Knowledge to Action Framework. This translation trajectory starts with the research phase and leads to dissemination and then implementation and institutionalization of the evidence. A missing piece of this framework is how health practice in the community can inform the development of interventions and research.
• CDC’s future directions in the National Cancer Program include health reform, primary prevention, policy change, protection of social justice, and enhanced surveillance and cancer registry applications (particularly for comparative effectiveness research). Partnerships and collaboration will be key to the accomplishment of CDC’s goals. Additionally, across all of its efforts, CDC will encourage programs and researchers to disseminate and implement their findings among all population groups.

DR. RICHARD PAZDUR:

THE ROLE OF THE PHARMACEUTICAL INDUSTRY IN THE NATIONAL CANCER  PROGRAM

Background

Dr. Richard Padzur has a distinguished career in clinical and academic oncology in addition to his experience as a regulatory expert at FDA. He has served as a practicing oncologist, researcher, and teacher at Wayne State University, where he was director of the medical oncology fellowship program, and at the M.D. Anderson Cancer Center at the University of Texas, where he was a tenured Professor of Medicine and Assistant Vice President for Academic Affairs. He joined FDA in 1999 as the Director of the Division of Oncology Drug Products and was named Director of the Office of Oncology Drug Products in April 2005. He has authored over 160 peer-reviewed papers in the field of oncology, has written chapters for over 30 oncology textbooks, and is the editor of two standard reference oncology texts.

Key Points

• The field of oncology has changed dramatically since the inception of the National Cancer Program in 1971. This transformation is due in part to the emergence of the pharmaceutical industry in the cancer field and the changing role of government in drug development.
• Government-supported drug development trials in the United States currently lack international perspective. The vast majority of applications the FDA receives for new drug approval contain drug development clinical trials and information that are international in scope.
• The internationalization of clinical trials does not create barriers but, rather, opportunities to develop drugs faster. For example, the NCI Clinical Trials Cooperative Group Program could partake in a collaborative effort with pharmaceutical companies in which NCI takes on the domestic components of a trial and the pharmaceutical company handles international accrual of the trial. Such a collaboration could also result in improvement in data quality. It is clear from the FDA perspective that pharmaceutical companies collect an excessive amount of data on clinical trials. On the other hand, trialists from other sectors, including the Cooperative Groups, may not provide all of the  necessary data for timely submission of a new drug approval. Having an active, ongoing collaboration with pharmaceutical companies for this endeavor might expedite drug development.
• There are many benefits to supporting international trials, such as faster trial accrual, especially for rare diseases. Having international access to patients will only become more important as oncology research delves deeper into defining molecular subtypes in smaller numbers of patients on clinical trials. In addition to having access to larger patient populations and faster accrual, international trials also provide information on drug efficacy in various ethnic populations. The U.S. has a large ethnic population, yet representation of these population groups is often missing in trials conducted exclusively in the United States. Additionally, internationalization of clinical trials allows integration of ideas from other countries.
• Pharmaceutical companies that are developing drugs on an international basis must comply with multiple drug regulators, not just FDA. FDA currently holds monthly teleconferences with the European Medicines Agency and Health Canada in an effort to establish relationships with other international drug regulators.
• The field of oncology drug development is also changing with the emergence of biomarkers. Biomarkers inform patient selection for clinical trials. They can also provide insight into drug disposition and activity and help relate these measures to clinical endpoints. Drug development should be partnered with biomarker development very early in the development of drugs or biologics. The use of biomarkers will result in greater efficacy in the population of interest and, possibly, smaller clinical trials.

DR. BARRY STRAUBE:

CMS AND THE NATIONAL CANCER PROGRAM: THE “TRIPLE AIM” GUIDEPOST

Background

Barry M. Straube, M.D., is Chief Medical Officer at the Centers for Medicare and Medicaid Services (CMS). Dr. Straube received an A.B. degree (magna cum laude, Phi Beta Kappa) from Princeton University and received his M.D. degree from the University of Michigan Medical School. He is board-certified in Internal Medicine and Nephrology.

Key Points

• The Centers for Medicare and Medicaid Services provides health benefits for more than 114 million Americans through Medicare, Medicaid, and the Children’s Health Insurance Program. In fiscal year 2011, CMS will spend $784 billion on these programs.
• The mission of CMS is to promote and ensure the health and health care of all their beneficiaries across the three aforementioned programs. A goal of CMS is to transform the agency from a passive payor/insurer of health to an active purchaser of high quality and value in health care. CMS follows a “triple aim” approach to improve health services, which focuses on population health, the experience of care, and per capita cost. CMS is particularly focused on reducing per capita costs while maintaining high-quality health outcomes. The agency has multiple drivers or tools to ensure a high level of quality and value.
• The first tool is contemporary quality improvement. Traditional quality improvement involves identifying a problem, measuring it, devising an intervention to improve quality of what is being measured, and implementing the intervention. Contemporary quality improvement entails evidence-based interventions, rapid-cycle quality improvement, and accountability. This concept can best be exemplified by the Quality Improvement Organization (QIO) Program. QIOs are private organizations that are staffed by professionals, mostly doctors and other healthcare professionals, who are trained to review medical care, help address beneficiary complaints about the quality of care, and implement improvements. CMS contracts with one organization in each state, as well as the District of Columbia, Puerto Rico, and the U.S. Virgin Islands to serve as that state/jurisdiction's QIO contractor. QIO contracts are three years in length. The current cycle began August 1, 2008, and includes a number of cancer quality improvement tasks focused on prevention and the use of health information technology.
• Early results after two years of the current QIO contract cycle reveal that over 96 percent of the 1,500 physician offices involved with the program are successful in reporting cancer rates and cancer screening rates via direct submission of records from electronic health records (EHRs). All offices using EHRs have been successful in increasing colorectal screening rates by at least 9 percent and breast cancer screening rates by a minimum of 6 percent. These rates were calculated against a control group of offices that do not track or report via EHR systems.
• The second CMS health improvement driver is transparency, which involves public reporting and making healthcare data readily available. CMS has  separate prospective payment systems used to pay for different clinical areas, such as doctors’ offices, hospitals, home health agencies, and nursing homes. Quality measures are being reported through a host of tools on CMS.gov that allow comparisons of different sites. Some CMS programs (e.g., physicians’ offices) have many cancer-related measures to report, whereas others (e.g., inpatient hospitals) have none.
• There is a gross need to develop more measures for quality of cancer care and treatment. Currently, the Hospital Inpatient Reporting Program has no cancer-related quality measures. The Hospital Outpatient Reporting Program has one cancer-related measure to report mammography follow-up rates. The Nursing Home program reports rates of chronic pain and post-acute pain, which abstractly link to cancer. The Home Health program only measures rates of pain control and Hospice Care reports symptomatic measures of some cancer types.
• CMS is sponsoring development of a host of cancer-related measures for the Hospital Outpatient Reporting Program. Some of these measures include: a companion measure of the rate of breast cancer detection following repeat imaging; adjuvant chemotherapy for colon and breast cancer; and needle biopsy to establish cancer diagnosis prior to surgical excision.
• In the physicians’ office program, there are currently 22 measures that address cancer-related diagnoses to some extent, but they are primarily process measures. Outcome measures and measures of patient experience of care are needed.
• The third health improvement tool CMS utilizes is financial incentives. Value-based purchasing is being implemented in hospitals, physicians’ offices, home health agencies, nursing homes, and other types of sites to promote higher quality of care. More money will be given to those clinical settings that exhibit better treatment and care outcomes, and less money will be given to those that have worse outcomes.
• Regulation is the fourth improvement driver. CMS writes conditions of participation or conditions for coverage for all clinical settings through which health care is delivered. These conditions set and demand basic levels of care and quality outcomes. A survey and certification process is implemented to ensure provider settings are compliant with the conditions. These regulations are a powerful tool that ought to be harnessed specifically to improve cancer care.
• The fifth CMS tool is coverage decision-making. CMS has an active role in the evaluation of published evidence regarding the effectiveness of diagnostic and therapeutic modalities in cancer care. Regular meetings of the Medical Evidence Development and Coverage Advisory Committee (MEDCAC) are held to elicit advice from scientific experts in a public forum. Recent MEDCAC meetings have been held on pharmacogenomics, biomarkers and cancer therapeutics, radiation therapy for prostate cancer, and screening computed tomography colonography for colorectal cancer. CMS also commissions technology assessments by the Agency for Healthcare Research and Quality and other organizations on cancer topics.
•  Some recent national coverage decisions related to oncology involve allogeneic hematopoietic stem cell transplantation (allogeneic HSCT), autologous stem cell transplantation (AuSCT), autologous cellular timmotherapy treatment for metastatic prostate cancer, cryosurgery ablation for prostate cancer, and liver transplantation for malignancy, among others.
• CMS also has a Medicare Clinical Trials Policy, by which costs incurred during treatment for clinical trials are paid. CMS will soon be implementing an FDA-CMS parallel review to streamline the coverage and approval of oncology drugs.
• Under the Affordable Care Act, CMS will be implementing the Center for Medicare and Medicaid Innovation (CMI). CMI will research new ways to encourage evidence-based coordinated care for CMS beneficiaries.

DR. MICHAEL KELLEY:

IMPROVING CANCER CARE: LESSONS FROM VA

Background

Dr. Michael Kelley, M.D., F.A.C.P., is National Program Director for Oncology at the Veterans Health Administration, U.S. Department of Veterans Affairs (VA). Dr. Kelley is also an Associate Professor of Medicine in the Hematology and Medical Oncology department of Duke University School of Medicine.

Key Points

• The Veterans Health Administration (VHA), part of the Department of Veterans Affairs, provides health benefits and care to the nation’s 24.8 million veterans. Currently, there are over 5 million veterans enrolled in the VHA; 95 percent of those enrollees are male. The VHA comprises 153 hospitals, 951 clinics, and 21 regional networks and provides care for approximately 3 percent of all cancer cases in the United States.
• Comparisons of care inside the VA system with that outside the VA have been conducted for an impressive number of diseases, including cancer. The results of these comparisons show that care in the VA is as good, if not better, on all the metrics used. The quality of VA health care is touted in Phillip Longman’s book, Best Care Anywhere: Why VA Health Care Is Better Than Yours.
• With regard to cancer, the main focus of the VA is on primary care—screening and prevention. Data from the June 2010 VHA Facility Quality and Safety Report reveal that women in the VHA system receive breast and cervical cancer screening at a rate at least 10 percent higher than outside of the VA. For colorectal cancer, the screening rate is 20 percent higher in the VHA than outside the VA system.
• The VA is particularly noted for its data systems, which entail a completely integrated and comprehensive electronic health record (EHR), a central cancer registry, and extensive administrative databases.
• The VA EHR system identifies patients, based on age, who may require specific health care services and alerts providers that those services are needed. These alerts arise in the Clinical Reminder Panel and the healthcare provider can then indicate that screening has been done, directly order screening tests, or indicate that the patient declines screening.
• High-quality health care requires healthy information systems. Effective electronic health systems support efficiency, virtual clinics, cancer registry data (e.g., identification of clinical trials), and patient centeredness. The VA systems allow patients access to EHRs at home or in the clinic or hospital. My Health e Vet (http://www.myhealth.va.gov) is a Web portal where veterans can access and download all of their health information.
• There is a great need to improve the clinical trials system across the country. Within the VA, the enrollment rate to NCI Cooperative Group studies is about half the rate of the rest of the United  States. However, the rest of the nation is not faring well, either; less than 1 percent of cancer patients enroll in NCI Cooperative Group trials. The barriers leading to these low enrollment rates include low funding, narrow enrollment criteria, and unintended effects of well-intentioned regulation. New regulations, from Institutional Review Boards (IRBs) or Health Insurance Portability and Accountability Act (HIPAA) privacy and security rules, reduce the number of trials approved, resulting in a loss of clinical trial expertise.
• Future therapeutic interventions in oncology must be “high yield,” meaning that they decrease mortality by at least 25 percent. Historically, some chemotherapy agents have improved survival by a much greater margin—chemotherapy agents for small-cell lung cancer improve survival by fourfold—than more recent therapeutic treatments that have been less and less effective in terms of improving survival.
• The few recent, successful high-yield therapeutic interventions have been biomarker-drug combinations specifically related to single genetic alterations and associated tyrosine kinase inhibitors. One such example is the development of the enzyme-inhibiting drug imatinib for treatment of chronic myelogenous leukemia. These successful biomarker-drug interventions need to be replicated and expanded to other tumor settings.
• The challenge with extending high-yield treatments to other cancer types is that many cancer cell mutations are pharmacologically difficult to target (e.g., ras, p53, p16 mutations). Overcoming this barrier requires alternative technological approaches to targeted cancer treatment, such as nanoparticles and siRNAs (small interfering RNAs), which both may soon become clinically applicable. When developing alternative interventions, cancer researchers must also consider that cancer types with multiple mutations may be susceptible to multiple drugs.
• A major barrier to biomarker-drug clinical trials is access to high-quality tissue specimens. The cost is high for obtaining tissue samples to conduct research on personalized therapies, and the use of bioinformatics to interpret trial results is very challenging. These barriers will become even more pressing to overcome as The Cancer Genome Atlas (TCGA) progresses. TCGA is a comprehensive and coordinated effort to accelerate understanding of the genetics of cancer using innovative genome analysis technologies.

DR. PETER GREVATT:

UNDERSTANDING EARLY-LIFE SUSCEPTIBILITY TO CARCINOGENS

Background

Peter Grevatt, Ph.D., is Director of the Office of Children’s Health Protection and Environmental Education, Environmental Protection Agency (EPA). He is also the Senior Advisor to EPA Administrator Jackson for Children's Environmental Health. He is responsible for ensuring that all EPA decisions are protective of children’s health and that EPA is an international leader on children’s environmental health issues. Dr. Grevatt served as the Senior Science Advisor in EPA’s Office of Solid Waste and Emergency Response and as the Senior Health Scientist in EPA’s Region 2 office. In these roles, Dr. Grevatt was responsible for ensuring that science, public health, risk assessment, environmental justice, and children’s health were fully considered in relation to a range of critical issues such as asbestos, polychlorinated biphenyls, lead, and arsenic. Dr. Grevatt led the National Water Quality Monitoring program in EPA’s Office of Water. More recently, as Director of the Economics, Methods and Risk Analysis Division in EPA’s Office of Resource Conservation and Recovery, he provided leadership to the regions and states on Resource Conservatio