Cancer Policy Monitor: April 2019
Cancer Policy Monitor – April 9, 2019
- Appropriations Update from Capitol Hill
- Big Changes This Spring Among Agency Leadership
- Gottlieb Leaves Legacy of Modernization and Reform at FDA
- FDA Releases Series of Cancer Clinical Trials Eligibility Guidances
- Registration Open for CAI Conference
- Reminder to Register for AACR/AACI Hill Day
- Registration Now Open for FDA-AACR Real-world Evidence Workshop
-Brandon Leonard, MA
President Trump released his administration’s budget proposal for fiscal year (FY) 2020 in March, formally kicking off the appropriations process. The president’s budget proposes a National Institutes of Health (NIH) funding level of $34.4 billion, which would represent a cut of $4.7 billion (12%) compared to FY 2019. The proposal would also cut funding for the National Cancer Institute (NCI) by $897 million (15%) to $5.247 billion.
These cuts would be enormously detrimental to medical research and cancer research in particular, but members of Congress in both houses and parties have made it clear they have no intention of slashing NIH funding. At an April 2 hearing on the NIH budget held by the House Appropriations Subcommittee on Labor, Health and Human Services (HHS), and Education, Chairwoman Rosa DeLauro (D-CT) and Ranking Member Tom Cole (R-OK) both made clear that the NIH remains a top priority for the subcommittee and that they expect to increase its funding in FY 2020. Their Senate counterparts, Subcommittee Chairman Roy Blunt (R-MO) and Ranking Member Patty Murray (D-WA), have also spoken strongly in support of increased NIH funding for FY 2020.
Also on April 2, House Democrats unveiled legislation to increase the budget caps for FY 2020. The bill proposes a $34 billion increase above the FY 2019 budget caps for non-defense spending and a $17 billion increase for defense programs. A bipartisan deal to lift the caps will be necessary to avoid large across-the-board cuts and to allow for increased investments in NIH and other priorities. The House Democratic proposal is a first step in what is expected to be a weeks-long negotiation on the budget caps.
The AACR is advocating for an increase of $2.5 billion for the NIH in FY 2020, for a total funding level of $41.6 billion. This request is broadly supported in the medical research advocacy community and is reflected in letters from both the Ad Hoc Group for Medical Research and One Voice Against Cancer. The AACR is an active member of both coalitions.
-Beth Russell, PhD
This April we will bring different, but familiar, faces at the head of the Food and Drug Administration (FDA) and the National Cancer Institute (NCI) as Commissioner Scott Gottlieb, MD, departs from the FDA and current NCI Director Norman “Ned” Sharpless, MD, moves over to FDA as acting commissioner. Meanwhile, current NCI deputy Director Doug Lowy, MD, will once again step into the acting director role at the NCI. Leadership changes can often be tumultuous times at the agencies; however, it is fortunate that both agencies will be in the hands of such recognized leaders and dedicated champions of cancer research.
Dr. Gottlieb made modernization, transparency, decisive action, and data-driven decision making the hallmarks of his tenure as FDA commissioner. Under Dr. Gottlieb, the FDA has begun a major reorganization designed to increase collaboration, merge operations activities, and increase emphasis on the work being done by the FDA Centers. Strategic hires, like Amy Abernathy, MD, PhD, as principal deputy commissioner, reflect long-term plans to modernize how the FDA uses data, including real-world evidence, for clinical trials and other regulatory decision-making. Dr. Gottlieb requested data from e-cigarette manufacturers on the role their marketing practices played in the current youth vaping epidemic. His swift and decisive action has brought the first steps on rulemaking surrounding flavored tobacco products and has set in action a plan for the FDA to study e-cigarette safety that will play a critical role in informing regulatory decisions surrounding these products.
Thanks to Commissioner Gottlieb, Dr. Sharpless will jump in as acting FDA commissioner to some of the same issues that he worked most ardently on at the NCI. Modernizing clinical trials and incorporating new and larger data sources into cancer science and care were hallmarks of his agenda for NCI that will be no less important in his new role at the FDA. His significant background in cancer and data science will also be instrumental in continuing the fight against nicotine addiction and tobacco-related diseases. In addition to his leadership at the NCI, Dr. Sharpless also previously served as director of the UNC Lineberger Comprehensive Cancer Center. Cancer medicine is a field rich in opportunities to touch on most aspects of biology, drug development, and public health that will serve him well at the FDA.
Dr. Sharpless leaves the NCI in the incredibly capable hands of NCI Deputy Director Doug Lowy, MD. Dr. Lowy previously served as acting director of the NCI from 2015-2017. During his two years as acting director, Lowy provided critical leadership to advance the National Cancer Moonshot Initiative for former Vice President Joe Biden and the Obama administration. He also oversaw the institute during the launch of the Genomic Data Commons and the Cancer Genomics Cloud Pilots, some of the most strategic data science efforts at the National Institutes of Health to date and cornerstones of the Cancer Research Data Ecosystem recommended by the Cancer Moonshot’s blue ribbon panel. This experience and his steadfast dedication to cancer research and care makes Dr. Lowy a superb choice to again lead the NCI as it continues to expand the role of data-driven decision-making in research and medicine.
-Nicole Boschi, PhD, and Trevan Locke, PhD
Earlier this month, Scott Gottlieb, MD, left his post as U.S. Food and Drug Administration (FDA) commissioner. Under his tenure, the FDA pursued many initiatives including important updates to e-cigarette regulation and modernization of drug review.
Gottlieb began work on his signature public health issue, nicotine addiction, two months into his tenure as commissioner. In July 2017, he began laying the foundation for the FDA’s Comprehensive Plan for Tobacco and Nicotine Regulation. In one of his first major speeches as commissioner, Gottlieb stated, “As a physician who cared for hospitalized cancer patients, and as a cancer survivor myself, I saw first-hand the impact of tobacco. And I know all too well that it’s cigarettes that are the primary cause of tobacco-related disease and death. What’s now clear is that FDA is at a unique moment in history, with profound new tools to address this devastating impact.” He directed the FDA’s Center for Tobacco Products to develop a comprehensive nicotine regulatory plan premised on the need to confront and alter cigarette addiction. This led to the development of the FDA’s Nicotine Steering Committee and began the rulemaking process to explore how to reduce nicotine in combustible cigarettes, whether to exempt premium cigars from regulation and how to regulate kid-appealing flavors in products like Electronic Nicotine Delivery Systems (such as e-cigarettes). Although youth e-cigarette use soared throughout his tenure, Gottlieb took several new actions, focused on both retailers and manufacturers, as part of his commitment to combat youth access to these products.
In addition to work in the tobacco space, Gottlieb oversaw the implementation of the 21st Century Cures Act and the establishment of the Oncology Center of Excellence (OCE), led by Richard Pazdur, MD. With support from Gottlieb, the OCE has led the way in modernizing clinical trials and the review of those trials. Under Gottlieb, the FDA released many new guidances to industry. These guidances covered topics including cell- and gene-based therapy, measurement of minimal residual disease, eligibility criteria for clinical trials, and more. As one of his final actions in office, Gottlieb began a large reorganization of the agency with a goal of creating an agency more capable of reviewing the increasingly interdisciplinary applications it is receiving. Among the changes, are new disease-centric divisions in the Office of Hematology and Oncology Products and the creation of the Office of Drug Evaluation Sciences.
Gottlieb was an avid and often candid spokesman for the agency he oversaw. Through social media, Gottlieb shared updates on regulatory publications and events, and he often provided explanations about topics or challenges the agency was facing.
-Beth Russell, PhD
In the lead-up to Commissioner Gottlieb’s impending departure from the U.S. Food and Drug Administration in early April, the agency released a flurry of draft and final guidances. Among them, five guidances on clinical trial eligibility for cancer patients were released. These guidances address eligibility criteria commonly applied to cancer clinical trials that result in exclusion of relevant populations. Patient populations considered in these guidances include:
- very young pediatric and adolescent patients;
- patients with organ dysfunction or concurrent malignancies;
- HIV, Hepatitis B, or C infection;
- and patients with brain metastases.
In the guidance from FDA, “Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials,” the agency addressed exclusion of children from clinical trials for new cancer drugs. Outdated eligibility criteria excluded pediatric patients from early-access to investigational therapies and resulted in limited pediatric-use information for drugs once approved. This guidance encourages that whenever possible and appropriate adolescents (12-17 years) be included in clinical trials for cancer drugs when the trial is disease or target-appropriate. Further, the agency provided instructions for dosing, drug activity and metabolism evaluation; safety monitoring; and ethical considerations. In the draft guidance, “Cancer Clinical Trial Eligibility Criteria: Minimum Age for Pediatric Patients Guidance for Industry,” the agency seeks public comment on striking the right balance between the minimum appropriate age for pediatric patients to be included in oncology clinical trials and safety of trial participants.
Other populations often excluded from cancer clinical trials are discussed in “Cancer Clinical Trial Eligibility Criteria: Patients with Human Immunodeficiency Virus, Hepatitis B Virus, or Hepatitis C Virus Infections; Draft Guidance for Industry” and “Cancer Clinical Trial Eligibility Criteria: Patients with Organ Dysfunction or Prior or Concurrent Malignancies; Draft Guidance for Industry,” which address eligibility criteria of patients with additional health considerations that have often lead to trial exclusion. In past, infectious diseases such as HIV or Hepatitis B, history of organ dysfunction, or a concurrent malignancy resulted in exclusion from cancer clinical trials for patients. Inclusion of such patients better reflects real-world populations but must be balanced with potential patient risk and variability in trial data. The FDA explains that careful evaluation of current health status could allow inclusion of such patients in cancer clinical trials.
On March 22, the FDA hosted a workshop co-sponsored by the National Brain Tumor Society to discuss another population often excluded from cancer clinical trials: patients with brain metastases. In the draft guidance, “Cancer Clinical Trial Eligibility Criteria: Brain Metastases,” the agency proposes shifting the eligibility paradigm away from wholesale exclusion of brain metastases from clinical trials and recommends that drug developers should provide rationale in the trial protocol if exclusion of patients with brain metastases is deemed necessary.
-Elizabeth Barksdale, PhD
On April 15-16, 2019, the American Association for Cancer Research will join the National Cancer Institute (NCI), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) in presenting the NIH-AACR Cancer, Autoimmunity, and Immunology Conference at the National Institutes of Health in Bethesda, Maryland.
Inaugurated in 2018, the Cancer, Autoimmunity, and Immunology Conference was created to delve into 1) understanding the biology of immune-related adverse events that have occurred in cancer patients treated with immunotherapies and how that might inform the study of autoimmune disease; and 2) defining the potential for the study of autoimmune disease to lead to greater understanding of the treatment and management of immune-related adverse events during and following cancer therapies.
The 2019 NIH-AACR Cancer, Autoimmunity, and Immunology Conference is being organized by:
- Elizabeth M. Jaffee, MD, 2018-2019AACR President; Deputy Director, Sidney Kimmel Comprehensive Cancer Center
- Elad Sharon, MD,
MPH, Senior Investigator, NCI
- Connie Sommers, PhD, Program Director, NCI
- Howard Young, PhD, Principal Investigator, NCI
- Katarzyna (Kasia) Bourcier, PhD, Program Officer, NIAID
- Marie Mancini, PhD, Program Director, NIAMS
This year, the NIH-AACR Cancer, Autoimmunity, and Immunology Conference will feature sessions focusing on gastrointestinal, neurological, and skin toxicities; and the use of pre-clinical models and meta-analyses for interrogating immune-related adverse events. Attendees will hear keynote presentations from Arlene H. Sharpe, MD, PhD, of Harvard University, on T-cell co-stimulation in autoimmune diseases and cancer; Elizabeth M. Jaffee, MD, of Sidney Kimmel Comprehensive Cancer Center, on immuno-oncology combination clinical trials; and Jennifer A. Wargo, MD, MMSc, of MD Anderson Cancer Center, on the link between the gut microbiome and immunotherapy response. See the full agenda.
Registration for this two-day conference is free. Those who cannot attend in-person can register to watch via webcast. There will also be a poster session following the main conference on April 15; the deadline to submit an abstract is April 10, 2019.
The AACR and the Association of American Cancer Institutes (AACI) invite you to Capitol Hill, Tuesday, April 30, 2019. This Hill Day will bring cancer center directors, researchers, physician-scientists, cancer survivors and other advocates to Capitol Hill to build support for a strong federal investment in biomedical research, and cancer research in particular, through the National Institutes of Health (NIH) and the National Cancer Institute (NCI).
-Elizabeth Barksdale, PhD
The American Association for Cancer Research (AACR) is partnering with the U.S. Food and Drug Administration (FDA) to present the Real-world Evidence Workshop on July 19, 2019, in Bethesda, Maryland. Real-world evidence (RWE) is clinical evidence generated from datasets including electronic health records, administrative claims data, patient-reported data, and genomics/biomarker data when collected in the routine provision of care. RWE has been lauded for its broad potential applications to improve clinical care, accelerate research, and support regulatory decision making.
Regulatory-grade RWE use cases span the drug development lifecycle, including early clinical development, clinical trials, and post-marketing and commercialization. To fulfill the Congressional mandate to further advance RWE, the FDA recently released the Framework for FDA’s Real-World Evidence Program.
This FDA-AACR workshop will discuss the agency’s work thus far on the implementation of that framework while exploring the current state of RWE in oncology. Speakers at the workshop will examine pre- and post- market use cases in which RWE was utilized to improve and accelerate treatment development and patient care and explore the potential of large genomic databases as real-world data sources. This event will also look to the future of RWE and consider how ongoing efforts will impact the oncology drug development landscape. See the preliminary agenda here.
The FDA-AACR Real-world Evidence Workshop is being organized by:
- Sean Khozin, MD, MPH,Associate Director, Oncology Center of Excellence, Director, Information Exchange and Data Transformation (INFORMED), FDA;
- Pallavi Mishra-Kalyani, PhD,Team Leader, Division of Biometrics V, Office of Biostatistics, Center for Drug Evaluation and Research, FDA; and
- Deborah Schrag, MD, MPH, Chief, Division of Population Sciences, Dana-Farber Cancer Institute.
Registration for this one-day workshop is free and open to the public.