2

The Current “System” of Cancer Control

The cancer control efforts of the United States are remarkably complex, and there have been many successes and setbacks. The system has evolved over time in a mostly undesigned way, with no overarching strategy or guiding vision of what an ideal cancer control system should operate or perform. The system is the product of hundreds of independent or near-autonomous cancer control efforts—research into the biology and epidemiology of cancer, improvements in surgery or radiation therapy, diagnostic and other product engineering, drug development and testing, hospice care, payment and reimbursement policies, and on and on. On various occasions, some organization, usually a government agency or professional group, has attempted to impose some sort of post hoc structure and direction on this system—such as by developing a “national cancer plan”—and to increase collaboration and coordination among the system’s various components. But, for the most part, the system still remains reactive with a near-term focus.

This chapter offers a brief overview of cancer control efforts pursued by different groups within the United States and around the world. The picture that emerges of the U.S. cancer control system is an amalgam of independent entities each possibly working toward a common goal but often not following a common strategic vision, with relatively little collaboration and cooperation with one another and with no overarching strategy that sets forth how these different components should be working together on cancer control.

GLOBAL EFFORTS IN CANCER CONTROL

Eighty-two percent of World Health Organization (WHO) member countries (158 nations) have established some form of high-level guidance system for cancer control, and these systems vary greatly according to the needs of their populations (Romero et al., 2018). The United Kingdom’s plan, for instance, places more emphasis on cancer prevention and survivorship care. Germany’s national plan prioritizes improving the early detection of cancers, increasing cancer care effectiveness and quality, and empowering patients within the medical system. Malaysia has recognized both conventional and complementary medicine for cancer control and has developed specific targets as part of its strategies for noncommunicable diseases (NCDs). Australia’s plan has centered on identifying effective indicators and standards for performance evaluation across all areas of cancer control. Canada’s recent plan has set milestones for cancer control subject to routine evaluations for a 30-year period. Peru’s cancer control plan has focused on expanding national funding within its public health system and providing universal health coverage for cancer care to the most vulnerable populations.

Japan’s plan for cancer control has prioritized improvements in clinical services, facilities, and registries as well as in related biomedical research (Hanyuda, 2012). China’s plan is designed to improve cancer registries, prioritize human papillomavirus (HPV) vaccine research and development, and advance the use of traditional medicines for prevention and treatment (Economist Intelligence Unit, 2015). India, the developer of one of the earliest national cancer control plans, has recently focused on establishing pain relief and palliative care networks throughout the subcontinent (Rath and Gandhi, 2014).

About 7.3 percent of total worldwide cancer deaths have been reported to occur in Africa (Bray et al., 2018). The various plans of African nations commonly include policies to curb tobacco use by taxation, raising the minimum age for purchase, and restricting related product marketing and advertising. As examples, Kenya’s recent plan has focused on improving cancer registries and surveillance practice, in addition to involving non–health sector participants in cancer control (Kenya Ministry of Health, 2017), and Rwanda’s national plan has focused on universal HPV vaccination coverage (Stefan et al., 2013). Table 2-1 provides a glimpse of the variation in all the countries with national plans for cancer control. Only about half of these national plans include an implementation strategy.

WHO and other agencies of the United Nations have issued a series of reports and resolutions describing the global threat of cancers and proposing ways to reduce the associated risks and burden. In 2005, WHO

TABLE 2-1 Proportion of Countries (n = 158) That Address Elements of Cancer Prevention and Control in Cancer-Related Plans, by Type of Plan

NOTES: NA = not applicable; NCCP = national cancer control plan; NCD = noncommunicable disease; Data for two countries that had plans other than NCD plans or NCCPs are not shown here; * For the policy relevance of tobacco as a risk factor for cancer, the questionnaire addressed whether or not a strategy for tobacco control was mentioned.

SOURCE: Table 1 in Romero et al., 2018.

passed a resolution on cancer prevention and control that urged member countries to create national plans to intensify their cancer control efforts. In 2013, WHO’s Global Action Plan for the Prevention and Control of NCDs gave an extra boost to cancer control efforts—as well as control efforts for other top NCDs such as cardiovascular diseases, chronic respiratory diseases, and diabetes—by setting the target of a 25 percent reduction in premature deaths resulting from NCDs by 2025 (WHO, 2013). That same year, the United Nations Development Programme launched an action plan against NCDs, including cancers. This action plan recognized NCDs as a significant challenge that impedes social and economic development (UNDP, 2013). Two years earlier, after pointing to the “growing danger” and “deepening crisis” of NCDs, the World Bank offered its own recommendations for reducing the rates of cancer, emphasizing increased taxation on tobacco products and providing subsidies for healthier food options (World Bank, 2011).

In another resolution issued at the 2017 World Health Assembly, the United States and other member countries, recognizing the urgent and more serious need to multiply efforts against cancer, adopted an “integrated approach” for cancer control (WHO, 2017), this time directly recognizing the core issues of affordability and availability of cancer interventions (UN, 2017).

FEDERAL EFFORTS IN THE UNITED STATES

Across the U.S. government, cancer control efforts are situated in a wide range of agencies, reflecting the very broad nature of cancer control. Within the Department of Health and Human Services, the lead agency with numerous constituent units interested in cancer, the Centers for Disease Control and Prevention (CDC), the Centers for Medicare & Medicaid Services (CMS), and the National Institutes of Health (NIH) warrant particular mention.

NIH has been a predominant funder and conductor of research and development related to cancer biology, prevention, detection, diagnosis, and treatment, especially through its National Cancer Institute (NCI),¹ while CDC’s focus has been to “develop, implement, and promote effective cancer prevention and control practices” (CDC, 2018a) in conjunction with state health agencies, territories, and tribes and tribal organizations. CMS manages the federally funded health insurance programs

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¹ A section of the National Cancer Act of 1971 authorized NCI to establish a national cancer program in cooperation with states and health agencies. The NCI director was to coordinate not only the cancer research programs within NCI but also all cancer control efforts related to other federal and nonfederal programs.

that provide coverage to millions of Americans, including those who are 65 years or older, eligible low-income families and children, pregnant women, and people with disabilities.

In addition to NCI, CDC, and CMS, there are a dozen more agencies within HHS whose research, policies, and programs are pertinent to cancer control. The Food and Drug Administration reviews drugs, biologics, and devices for cancer diagnostics and treatment (FDA, 2018). The Office of Population Affairs administers the Title X program on population health, including a program for breast and cervical cancer screening and prevention (HHS, 2018). The Health Resources and Services Administration coordinates the National Center for Health Workforce Analysis, which collects workforce data, develops tools for projecting workforce supply and demand, and evaluates workforce policies and programs (HRSA, 2019). The agency also oversees several cancer-relevant federal programs and initiatives, including the 340B drug discount program.² The Agency for Healthcare Research and Quality performs and funds research to improve the quality, safety, efficiency, and effectiveness of medical services and makes those findings publicly available (AHRQ, 2019). The Indian Health Service ensures that culturally appropriate cancer services and surveillance are available and accessible to American Indian and Alaskan Natives to reduce health disparities and ultimately reduce cancer burden (IHS, 2019).³

The Department of Veterans Affairs (VA) has conducted cancer research since 1932 (before NCI even existed), when it established its first tumor research laboratory. Recent census data indicate that there are nearly 18.2 million veterans of military service in the United States, half of them over 65 years of age (Census Bureau, 2018). VA provides medical care for approximately 3 percent of U.S. cancer cases each year through the Veterans Health Administration (Zullig et al., 2017). Through the Million Veteran Program, launched in 2011, VA has focused its efforts on gaining a better understanding of how genetic and other variations influence cancer risks and burdens among veterans. Furthermore, as a partner in NIH’s All of Us, VA has sought to ensure veteran participation in this research program.

Additional federal agencies involved in cancer control are the Department of Defense (DoD), Department of Energy (DOE), Environmental Protection Agency (EPA), Department of Agriculture (USDA), Department of Education (ED), Department of the Treasury, Department of Labor (DOL),

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² The 340B drug discount program was created by Congress in 1992 with the goal of improving patients’ access to outpatient medications by allowing hospitals and clinics that serve high volumes of low-income patients to purchase drugs at discounted prices.

³ This text has been revised since prepublication release.

Department of Housing and Urban Development (HUD), Department of Commerce (DOC), Office of Management and Budget (OMB), Equal Employment Opportunity Commission (EEOC), Social Security Administration (SSA), and Office of Personnel Management (OPM). Brief descriptions of these agencies’ activities follow.

DoD has carried out and provided external funding for cancer research through its congressionally directed medical research programs to support members of the military and their beneficiaries (DoD, 2015). In 1992, with congressional funds, DoD started a breast cancer research program, followed 5 years later by a prostate cancer research program. Subsequently, the congressionally directed medical research programs have expanded to include research on lung, kidney, and ovarian cancers. In addition, the Big Mechanism program, launched in 2014 by the Defense Advanced Research Projects Agency, is aimed at developing automated technologies to understand the biology of cancer as well as the complex interactions that lead cells to become cancerous (Cohen, 2015).

DOE and NIH jointly coordinated the Human Genome Project, which helped advance the scientific understanding of human genetic variation and its impact on population health. In 2018 the agency entered into a new partnership with NCI to launch the Joint Design of Advanced Computing Solutions for Cancer, with the intent of accelerating advances in precision oncology and related computing technologies (DOE, 2018).

EPA has set air and water quality standards since the Clean Air Act of 1970 and the Clean Water Act of 1972. The agency has determined the health hazards of chemical contaminants that may be present in the environment. In addition, EPA manages the integrated risk information system, an electronic database that contains information on human health effects from exposure to certain substances in the environment (EPA, 2018). Furthermore, EPA publishes information on the likely carcinogenic effects of exposure to various contaminants and pollutants in the environment.

USDA’s principal involvement in cancer control has been to address a range of food safety issues. The agency’s responsibilities include ensuring that the nation’s commercial supply of meat, poultry, and egg products is safe, healthful, and correctly labeled and packaged (USDA, 2018a). The agency provides statistical information, including agricultural chemical usage data, related to the safety of the U.S. food supply. Also, every 5 years USDA and HHS jointly publish the Dietary Guidelines for Americans, which has been used to guide various other federal policies and programs, including the Supplemental Nutrition Assistance Program (USDA, 2018b), which currently serves 42 million people (CBPP, 2018), and the National School Breakfast and Lunch Programs, which serve more than 30 million students daily (USDA, 2018c).

ED plays an important role in health literacy by collecting and reporting data on health literacy, which has been associated with health outcomes (poor health literacy generally being associated with worse outcomes). According to an ED-commissioned analysis, only 12 percent of adults have a functional level of health literacy (Kutner et al., 2006)—a concern both for individuals wishing to understand the nutrition or treatment options that best meet their needs and for policy makers choosing among several health policy options. The lack of basic health literacy could overwhelm cancer patients needing to absorb an abundance of complex information throughout their care. Schools may offer partial support to alleviate this concern (which has been, as noted earlier, recognized by the United Nations Development Programme). In the United States, nearly 57 million young people are enrolled in elementary and secondary schools each year (NCES, 2018). Schools in many states already have standards in place for health education to help students learn skills to make healthful choices throughout their lifetimes, but making informed decisions during cancer treatments still remains a complex process for patients and their families.

Within the Department of the Treasury, the Alcohol and Tobacco Tax and Trade Bureau regulates the production, importation, distribution, labeling, and advertising of tobacco and alcohol—both of which are known risk factors for several malignancies. To limit the consumption of these significant cancer risk factors, the agency levies and collects excise taxes on them; however, the full effects of these tax policies on tobacco and alcohol use across the United States remain to be well characterized. Since the annual tax revenues from tobacco have been decreasing—in 2010 it was $17 billion, while in 2017 it was $14 billion—this would seem to indicate that there has been a general decline in cigarette smoking (Statista, 2018b). By comparison, revenues from alcohol sales and consumption increased over the same time, from $9.2 billion in 2010 to nearly $10 billion in 2017 (Statista, 2018a).

DOL manages workforce concerns related to employee rights and safety and also administers compensation programs for government employees—for example, DOE workers—whose work exposes them to radiation. The Bureau of Labor Statistics (BLS) publishes and maintains labor market trends. The agency has projected that the supply of physicians and surgeons will grow by 13 percent from 2016 to 2026, which is much faster than the average for all occupations. The demand for more clinicians has been expected to increase, given the aging population (BLS, 2017), but one particular analysis predicted the demand for oncology services to grow by 40 percent, whereas supply of clinicians may only grow by 25 percent through 2025 (Yang et al., 2014).

HUD’s principal involvement in cancer control has been to address a wide range of environmental health and safety concerns (HUD, 2009).

The agency has implemented smoke-free policies in all its properties. In 2018, HUD expanded its mandatory no-smoking policy to all public housing and work facilities, banning the use of tobacco products in not only individual units but also common areas.

While the DOC’s responsibilities are broad—it oversees international trade agreements and sets technology standards, for example—of particular relevance to cancer control is the role of its U.S. Patent and Trademark Office (USPTO). In 2016, USPTO launched the Patents 4 Patients initiative (also known as the Cancer Immunotherapy Pilot Program) to provide an accelerated review of patent applications for cancer immunotherapy technologies without a petition fee (USPTO, 2018). Between 2007 and 2017, nearly 5,400 patents were issued for cancer applications.⁴ However, the bulk of these new patents have been criticized as business tactics for maintaining product market exclusivity, with claims that offer only marginal improvements and modest—or even decreased—clinical benefits to the patients who receive those drugs (Chen and Kesselheim, 2017; Hitchings et al., 2012).⁵

OMB assists the White House in setting funding priorities and in financial management across the executive branch (OMB, 2019). This broad responsibility deserves particular mention, as the OMB decisions could influence the variety and degree of cancer control activities pursued by many federal agencies. For example, since 2013, OMB’s 2 percent budget sequester cut to Medicare Part B affected cancer drug reimbursement (Rosso and Davis, 2018).⁶

EEOC enforces federal laws that prohibit discrimination and harassment in the workplace. The agency enforces laws that make it illegal for private companies and federal, state, and local governments to deny a qualified job applicant a position because of a disability. Cancer patients and cancer survivors are more likely to report disputes related to job termination, terms and conditions of employment, and benefits than individuals without cancer (McKeanna et al., 2007). EEOC issues guidance on the workplace rights requiring employers to provide “reasonable accommodations” for individuals who are undergoing cancer treatments

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⁴ Results of a search in the U.S. Patent and Trademark Database with the search strategy “TTL/cancer and ISD/20070101->20173112,” from 2007 to 2017.

⁵ Patents have also been sensed as a pivotal force and interact with health insurance in increasing costs of the drugs by evaporating the normal market forces. In addition, many drug patent holders employ a number of strategies, including “evergreening” and “pay for delay,” to lengthen market exclusivity for their products, a topic discussed in Making Medicines Affordable: A National Imperative (NASEM, 2018).

⁶ Several professional organizations, including the Community Oncology Alliance, have consistently filed lawsuits intended to stop CMS from applying the sequester cut because of the potential it has to shift care from community setting to outpatient hospital systems.

or have survived cancer. Such accommodations include modified work schedules or spaces for employees with cancer.

SSA offers financial support programs for thousands of cancer patients who apply for disability benefits every year. Currently, an approval of cancer-related disability claims entails a multistep process determined by the agency, based on medical reports regarding the severity of the condition and functional assessments (SSA, 2018).

OPM has the responsibility to support employee wellness, manage leave provisions, and minimize overall medical costs for the U.S. government (OPM, 2018a), which is the largest employer in the United States and spends more than $53 billion per year in medical benefits for employees and retirees (OPM, 2017). Through the Federal Employees Health Benefits Program, OPM’s preventive health services coverage includes screening for breast, prostate, cervical, and colorectal cancers. The agency also provides sick leave for federal employees and their family members for conditions that require hospitalization, inpatient care, or continuing treatment. OPM’s work site wellness programs and other initiatives across most federal agencies include help with smoking cessation, alcohol control, diet, and nutrition (OPM, 2018b).

From this sampling, it is clear that most of the leading agencies in the U.S. federal government—and not just those with a traditional focus on health research, wellness promotion, and disease control—are involved in cancer control efforts. And because cancer control is a complex adaptive system, the effects of these individual agencies spread widely beyond their nominal areas of responsibility.

STATE AND LOCAL INITIATIVES

The U.S. federal government has directly relied on states to design and conduct field programs for cancer control. For nearly a century, states have been recognized as principal actors for implementing a number of federal acts and initiatives on cancer, although generally without clear specifications or an overarching charter to consolidate their efforts. The National Cancer Act of 1937 required the newly formed NCI to “cooperate with state health agencies in the prevention, control, and eradication of cancer” (NCI, 2018a). The National Cancer Act of 1971 also empowered states to establish cancer control programs in collaboration with NCI (NCI, 2018b). State and territorial health departments are also periodically consulted in the formulation of the objectives for the Healthy People Initiative, a decadal priority-setting exercise for disease prevention and control. (The cancer-related goals for 2020 are listed in Box 2-1.)

Over time, as the number of participants and communities involved in cancer control efforts kept increasing, it became clear that it was not

enough simply to set national goals and leave it up to the multiple interested parties to determine on their own what they would do in pursuit of these goals—or even if they would pursue those goals at all. In 1998, CDC began a pilot program to promote a more “comprehensive” approach to cancer control across state, territory, and tribal administrations. In that program, CDC funded five states (Colorado, Massachusetts, Michigan, North Carolina, and Texas) and one tribal health board (Northwest Portland Area Indian Health Board), each of which already had established a cancer control plan for its jurisdiction (Major and Stewart, 2009). Cancer plans have since proliferated, and today all 50 states and the District of Columbia, 6 U.S. Pacific Island jurisdictions and Puerto Rico, and 8 tribes and tribal organizations have cancer plans in place—in total, 66.⁷ Each

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⁷ This text has been revised since prepublication release.

plan has a local focus with whatever differences are necessary to meet local needs created by cancer burden (CDC, 2019). What is unknown is how many more unwritten, unpublished, and informal plans or guidance documents exist.⁸

CDC has determined that these plans should focus on encouraging people to make healthy choices, educating people about cancer screening tests, increasing access to high-quality cancer care, and reducing health disparities. Additionally, CDC guidance encourages plans to improve quality of life for cancer survivors, to implement changes in policies and local environments in order to promote healthy behavior, and to demonstrate outcomes through performance evaluation. It is difficult to determine whether every state pursues exactly these priorities because each state has different areas of focus, different implementation methods, different performance evaluations of their programs, and different approaches to refining and updating their plans.

Additionally, the states seem to differ on what they actually recognize as being part of the cancer control “continuum.” For Arizona, the continuum includes prevention, early detection, diagnosis and treatment, quality of life, and cancer research. Alaska includes “health promotion and advocacy” and “system-level evaluation and surveillance efforts” in addition to prevention, screening and early detection, diagnosis, treatment, and survivorship. Georgia emphasizes “palliative care as needed for those living with a cancer diagnosis” along with prevention, screening and early detection, diagnosis and treatment, and survivorship.

The levels of detail in the various state cancer plans are also highly variable. In addition to high-level goals and strategies, Florida’s plan also includes a variety of data sources to clarify cancer burden and apply interventions demonstrated to be useful; it also provides information on some national cancer screening guidelines. Hawaii’s plan does not have explicit cancer control goals for exercise or nutrition, although these goals do appear in a companion plan focused solely on achieving them. Many state plans have a 5-year time horizon and may call for a “review” at the end of that period. The District of Columbia plan has some form of annual reviews built in over the course of its 5-year duration to aid in refining the plan as time goes on.

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⁸ For the sake of comparison, there is one national plan for cardiovascular disease, which is the number one cause of death in the United States. In 1998, Congress charged CDC to develop a national plan for heart disease and stroke and to promote the implementation of the plan in every state and U.S. territory. With the current iteration of the plan, CDC aims to help promote the achievement of national goals for preventing heart disease and stroke through 2020 and beyond.

A desired standard for a cancer control plan—or any strategic plan for health or business, for that matter—is that the goals be specific, measurable, achievable, relevant, and time bound. Some states, however, do not develop such goals for their cancer control programs, and even when such goals have been set, they are often idiosyncratic and specific to a particular state. Therefore, it is difficult if not impossible to compare goals across states and to see what kind of accountable progress is being reported from different parts of the country. A content review of the state cancer control plans revealed that Michigan, New York, and Montana, among a dozen other states, use the baseline numbers from their states’ Behavioral Risk Factor Survey System (BRFSS) and Youth Risk Behavior Surveillance System (YRBSS) to set their goals and targets. For instance, to further reduce the use of tobacco products, Michigan’s recently set goal is to reduce the use of smokeless tobacco products by adults and adolescents from 11.8 percent (adults) and 6.9 percent (adolescents)—the baseline values reported in the Michigan BRFSS and the YRBSS—to 10.6 percent (adults) and 6.2 percent (adolescents) by 2020. In New York, the goal is to decrease the percentage of adolescents in grades 9–12 who use any tobacco product, including e-cigarettes, from 25.4 percent—the baseline reported in the 2016 New York State Youth Tobacco Survey—to 17.7 percent by 2023. Maryland’s targets are based on information from the Healthy People Initiative along with the Maryland BRFSS and the Youth Tobacco and Risk Behavior Survey.

PERFORMANCE EVALUATION

A foundational hurdle affecting the progress of state and local cancer control programs is that currently there are no agreed-upon or declared national⁹ standards or methods (including for data analyses) for evaluating the performance of their cancer control plans. Each state agency, along with its coalitions or partners, is responsible for monitoring and updating its particular plan, often using standards that may be implicit or ad hoc. Furthermore, the revisions or updates—which may happen every 5 or so years, depending on the state—are generally based on some form of survey input from a wide range of participants in the state, and outside consultants may be hired to help revise and update the plans (Hager et al., 2010).

Two main techniques have been used to measure progress. In the first, the state cancer registries are consulted for data on the most recent patterns of cancer incidence, treatment, and mortality. In the second,

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⁹ This text has been revised since prepublication release.

data from the BRFSS,¹⁰ the YRBSS,¹¹ National Immunization Surveys,¹² or the National Health and Nutrition Examination Survey (NHANES)¹³ are consulted for patterns of health related behaviors that increase one’s risk of cancer.¹⁴

Since the launch of its National Comprehensive Cancer Control Program, CDC has worked toward developing performance measures for state and local cancer plans and identifying areas of achievement as well as areas where assistance is needed (Rochester et al., 2011; Townsend et al., 2015). To develop consistent performance measurement methods, CDC established an advisory group of stakeholders and commissioned a consulting firm to prepare and implement a “logic model” that outlined structure, process, and outcome domains that might be useful for performance measures. The final worksheet produced nearly a dozen measures grouped under four main areas: engagement of stakeholder organizations, programmatic elements, funding levels, and policy outcomes. The measures have been refined over the years to clarify survey questions and strengthen indicators to more accurately measure program activities and outcomes (Townsend et al., 2015). The measures provide information about the components of the plans and their activities, the composition of the cancer control coalitions and their satisfaction, the number of objectives of the plans, and the source of their surveillance data. However, they are not able to provide meaningful information about which of the activities may not be effective and for what reasons.

The state plans have experienced mixed results, but some beneficial outcomes have been documented, including increased screening and vaccination rates and better identification of cancer survivor needs (Given et al., 2010, 2018; Rochester et al., 2010). To date, no professional organization has conducted or commissioned an objective, neutral performance analysis of all the goals proposed and implemented by state cancer control plans. On its own or under congressional directives, the Government Accountability Office (GAO) has examined the

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¹⁰ The BRFSS is a state-based system of telephone health surveys that collects information monthly about U.S. residents regarding their health-related risk behaviors, use of preventive health practices, and health care access related to their chronic health conditions.

¹¹ The YRBSS includes national, state, and local surveys conducted every 2 years to monitor the health risk behaviors among students in grades 9–12 that contribute to morbidity and mortality in both adolescence and adulthood.

¹² These surveys are a group of phone surveys used to monitor vaccination coverage among children 19–35 months and teens 13–17 years and flu vaccinations for children 6 months–17 years.

¹³ NHANES includes a series of cross-sectional nationally representative health examination surveys conducted in mobile examination units or clinics to assess the health and nutritional status of children and adults in the United States.

¹⁴ This text has been revised since prepublication release.

performance of federal health programs with particular relevance to cancer control efforts (see Box 2-2), and various changes were made in response to the GAO findings.

A VIGOROUS SYSTEM OF PARTICIPANTS AND INTERESTS

Complementing governmental efforts are hundreds of groups with diverse missions and interests, which have vigorously expanded activities for cancer control. Biopharmaceutical and medical device industries, philanthropic groups and foundations, professional organizations, academia and research organizations, employers, and, more recently, information, consumer, and financial technology companies all bring their niche, interests, and resources to this vibrant system of participants.

Currently, all large biopharmaceutical companies manufacture oncology products. Investment in cancer drug research and development has been growing strongly, forecasted to reach $100 billion by 2022 (IQVIA, 2018). Nearly 700 organizations—ranging from academic incubators and small biopharmaceutical companies with a single drug candidate to large companies with a bigger portfolio of drug candidates—have one or more oncology drugs in late-stage development (IQVIA, 2018). Oncology drugs currently represent 40 percent of the global therapeutic pipeline (Albrecht et al., 2018). And cancer products continue to dominate clinical trials—in 2017 one in every four completed industry-sponsored clinical trials was in oncology (Albrecht et al., 2018).

Funding from philanthropies and foundations for cancer control activities has also increased. One of the oldest cancer philanthropic organizations, the American Cancer Society (ACS)—created in 1945 as a successor to the American Society for the Control of Cancer—has strategically employed public relations, fund-raising, and other dynamic strategies to create a greater public demand for action on cancer. Indeed, the notion of cancer control as a “moon shot,” a “winnable war,” or a “crusade” was largely framed through the persistent advocacy of ACS.

Currently, nearly half of registered charities and nonprofit organizations involved in disease research, management, or advocacy in the United States are cancer related (GuideStar, 2019). These organizations generally have very narrow interests—a particular organ or tissue, a particular type of cancer, or some specific aspects of cancer control. There are multiple nonprofits focused on breast cancer, prostate cancer, lung cancer, and hospice care. Not all these “cancer” organizations have a background in medicine or population health, nor do they approach cancer control efforts through those lenses; many of them focus on socioeconomic and social justice issues or on political activism, while others are

purely focused on the financial aspects of cancer control. Box 2-3 briefly reviews some of the roles the numerous patient advocacy groups play.

Additionally, religious institutions and faith-based organizations have played a variety of roles in cancer control (Campbell et al., 2007). Places of worship have long provided social network support to cancer patients within their congregations, chiefly through prayers, scriptural readings, and spiritual support. Many religious organizations regularly organize free cancer screening and cancer awareness programs (DeHaven et al., 2004).

Employers are paying greater attention to cancer control as they look for ways to improve the health of their employees while managing their contributions to costs for cancer care and other diseases (BLS, 2018; Isehunwa et al., 2017; Mattke et al., 2013). Box 2-4 briefly explores this topic.

There are dozens of cancer-related professional and membership groups as well. One estimate offers a listing of nearly 58 such professional societies (CancerIndex, 2017). These various organizations frequently publish clinical practice guidelines and policy priorities for cancer control. These guidelines, as discussed in Box 2-5, often apply varying standards for evidence generation and use and sometimes make conflicting recommendations.

CONSUMER AND OTHER TECHNOLOGY FIRMS IN CANCER CONTROL

A rapidly evolving change in the U.S. health and medical system relates to the increasing direct investments and acquisitions of information, consumer, and financial technology firms by other, generally larger

companies. Alphabet, Amazon, Apple, Facebook, GE, Google, IBM, Intel, and Microsoft are among the large companies that have active investments in health care projects, viewing this area as the next big “information business.” A 2016 news report conservatively estimated that at least $40 billion in collective investment had been made by a handful of these companies (Schwartz, 2016). Coalitions have begun to emerge among wealthy donors, finance firms, and publicly traded companies, such as a recently formed entity involving Amazon, Berkshire Hathaway, and JPMorgan Chase. Google has been investing in drug development start-ups (Reuters, 2018), Intel has invested in predictive analytics companies working on noninvasive colon cancer screening (CB Insights, 2018), and

Microsoft is investing in improved cancer diagnostics (Microsoft News Center India, 2018). Many of these companies also bring to bear significantly advanced computational capabilities previously unavailable for any application in society.

In the next decade or so, if forecasts are correct, the already complex cancer control system will gain an entire new layer of complexity with the large-scale aggregation of genomic, environmental, behavioral, and other information from representative patient populations. The purpose of collecting these vast amounts of diverse data is to enable the creation of treatments tailored to the unique biology of individual patients. Underlying these initiatives are new computational capabilities for rapidly conducting

whole-genome sequencing, identifying novel associations (e.g., through machine learning), and linking these associations to patient outcomes. With large patient databases, it is also possible to understand whether unusual treatment responses identified in small patient populations point toward previously unrecognized patient populations who could benefit from tailored treatments (Chakradhar, 2016).

In the past decade, several major public and private ventures have been launched with the goal of creating repositories of genomic data that can be sequenced and analyzed. The NIH Cancer Genome Atlas, launched in 2006, has the goal to “generate, quality control, merge, analyze, and interpret molecular profiles at the DNA, RNA, protein, and epigenetic levels for hundreds of clinical tumors representing various tumor types and their subtypes” (Weinstein et al., 2013). By the end of the program in 2018, the Cancer Genome Atlas had mapped nearly 20,000 specimens spanning 33 cancer types (NCI, 2019). The Cancer Genome Atlas Research Network has provided the infrastructure (through joint funding by NIH and European agencies) to archive these data (Tomczak et al., 2015). Along with NIH’s All of Us program, VA’s Million Veteran Program, and nongovernmental programs such as the Oncology Research Information Exchange Network, there seem to be numerous promising opportunities to harness computation tools to advance cancer control. Google’s Verily, for example, has already demonstrated a proof of concept for using “deep learning” approaches to identify the location and size of a breast cancer tumor in a way that can outperform human radiologists (Dobush, 2018).

The inevitable rise of such large-scale data approaches to cancer research will require further efforts to develop aggregation infrastructure to share these insights widely. However, these data collection and storage mechanisms have begun to raise a host of questions related to equity (e.g., Who benefits from the new knowledge?), access (e.g., Do patients have the right to refuse the uses and reuses of their data?), and commercialization (e.g., Do all uses of data need to have an altruistic objective, or can these data be used for private, commercial benefit?).

HISTORICALLY COMMON THEMES

Several themes have commonly appeared and been regularly repeated in discussions on cancer control over the past couple of decades. Drawing on previous publications of the National Academies, six of those common themes are summarized in this section.

The first theme is the very “fragmented” nature of cancer control efforts—one that affects patients in significant ways and makes it logistically challenging to coordinate actions across the cancer control continuum, including prevention, screening and early detection, diagnosis,

treatment, palliative care, survivorship care, and hospice care (IOM, 2001a, 2003a,b, 2006, 2007, 2008, 2013a,b, 2015). The usual recommendations to address this fragmentation have been to encourage better integration and coordination among cancer programs, hospital and social services, and clinicians and to provide more funding from government and private agencies to drive that coordination. Two reports, for example, made identical recommendations that funding agencies should support work to enable continuous coordination between cancer treatment and survivorship care (IOM, 2003b, 2006). Other recommendations have called for consistency among clinical practice guidelines and assessment tools.

The second theme is improving cancer prevention and early detection. Recommendations have included expanding screening programs, increasing vaccination rates, and promoting public awareness and education (IOM, 2001a, 2003a, 2007; NASEM, 2016a). Insurance companies have been encouraged to provide coverage for cancer prevention and early detection (IOM, 2003c), and federal and state agencies have been urged to expand community-based programs that provide hepatitis B screening, testing, and vaccination services (IOM, 2010b). There have also been regular calls for increased public–private partnerships to promote healthy lifestyles.

The third theme is the availability and use of a “data infrastructure”—an issue that routinely comes up not only in discussions on how to understand and improve cancer control efforts but also in more general discussions about overall medical care and health policy. “There is no national cancer care data system in the United States,” concluded an Institute of Medicine report issued in 2000 (IOM, 2000a). Today, there is still no such system. Frequently cited reasons for the lack of such a data system include the absence of recognized quality measures, the absence of benchmarks to measure progress, and concerns about the confidentiality and security of patient information. Various recommendations have called for improving regulations governing the collection and use of clinical patient data (IOM, 1999, 2000a, 2014), while another typical recommendation has called for the development of “patient portals” to enhance data sharing and communication among clinicians, patients, and families (IOM, 2013a). The development of a data infrastructure that is widely available can be seen as a separate approach to increasing coordination—another goal that appears repeatedly in various forms.

A fourth theme concerns the persistent health disparities that exist in cancer control. Specific recommendations have been to identify and disseminate effective community interventions, to support public–private initiatives to reduce disparities in the cancer burden, and to develop specific programs and initiatives to increase access to medical services (IOM, 1999, 2013b). There have also been calls to ensure consistent

implementation of current standards of care and measurement of quality metrics (IOM, 2003b, 2013b; NASEM, 2016a).

A fifth theme is the importance of biomarkers and new technologies for chemoprevention, early detection, disease classification, drug development, treatment planning, and monitoring and surveillance (IOM, 2001b, 2003a, 2007, 2010a). Biomarkers are essential for the success of precision medicine approaches to cancer treatment (NASEM, 2016b), which aim to improve the safety and effectiveness of interventions by increasing response rates, reducing adverse effects of therapy, and increasing patient adherence to treatment regimens (Burnette et al., 2012; Collins and Varmus, 2015; Love-Koh et al., 2018; Savoia et al., 2017; Snyderman, 2014). However, precision medicine has also been met with some skepticism about whether its potential to improve patient outcomes can be fully achieved. A 2016 National Academies report on biomarker tests for precision medicine emphasized the importance of standards for evidence generation, oversight, payment models, and decision making for test development and use in clinical care (NASEM, 2016b).

The absence of agreement on the precise definition of precision approaches—now being extended to prevention—also poses uncertainty from a regulatory and reimbursement standpoint (Degtiar, 2017; Faulkner et al., 2012). Another challenge in achieving the goals of precision medicine is that precision approaches do not typically consider the larger social environment of the individuals—a factor that some consider to be at least as influential as genetics for the design of various treatments (Bayer and Galea, 2015; Carlsten et al., 2014; Juengst et al., 2016; Minari et al., 2018). One argument for greater investments in population health—versus precision medicine—seems to stem in part from the disparities in the occurrence and outcomes of disease as noted above, with certain groups more likely to develop the disease or less likely to receive effective treatment or both.

The sixth theme is about making cancer research and care more effective and efficient (IOM, 2000b). Recommendations have focused on improving the process of conducting large-scale biomedical research (IOM, 2003d), developing guidance on reimbursement decisions (IOM, 2006), determining the factors that put individuals at high risk for poor physical and psychosocial outcomes (IOM, 2008), identifying effective ways to communicate accurate cancer risk information and statistics to patients and other stakeholders (IOM, 2012), and enabling the broader enrollment of patients in clinical trials (IOM, 2010c). All six themes have been linked to calls for more research and more coordination.

PUBLIC TRUST IN CANCER CONTROL

New discoveries often spur changes in clinical and public health practice, drive the creation of new academic subfields, and shift funding priorities for research and product development. Some putative discoveries, however, have later been shown to be irreproducible, ultimately setting back scientific progress and delaying potential benefits for patients. A growing body of evidence indicates that study findings in the biomedical, public health, and social sciences often cannot be replicated. This is a topic of active concern in the scientific community and policy circles.

In a recent survey, greater than 70 percent of researchers reported that they had tried and failed to reproduce another researcher’s experiments at some point. In addition, greater than half of the researchers had failed to reproduce some of their own experiments (Baker, 2016). This issue of reproducibility further complicates the clinical guidelines debate and raises concerns about whether the right kinds of investments are being made in research and whether research is accountable and responsive to such investments, often coming from taxpayers (An, 2018). A recent report on reproducibility and replicability in science recommended that “scientists should take care to avoid overstating the implications of their research and also exercise caution in their review of press releases, especially when the results bear directly on matters of keen public interest and possible action” and that “anyone making personal or policy decisions based on scientific evidence should be wary of making a serious decision based on the results, no matter how promising, of a single study” (NASEM, 2019).

False-positive results stem from two factors: a lack of statistical power and experimental or investigator bias. Recent analyses have shown that false-positive results are even more likely to appear in circumstances where multiple research teams are simultaneously testing the same hypothesis (e.g., in genome-wide sequencing studies), where it is likely that at least one research team will find a significant result purely by chance (Ioannidis, 2005). Compounding this challenge is the fact that the scientific community and the current academic incentives tend to reward positive findings more strongly than negative findings, which might motivate a minority of researchers to inappropriately manipulate study designs or misrepresent data in ways that increase the chances of obtaining positive results (recognized in the scientific community as misconduct, similar to data fabrication) (NASEM, 2017). Several aspects of study design can contribute to bias and false-positive results. For example, findings with small effect sizes (even when statistically significant) are more likely to be false-positive results. In addition, allowing for more flexibility in design, definition, and acceptable testing strategies can also lead to post

hoc, arbitrary changes to study design that can alter results (known as “phacking”) (Ioannidis, 2005). For example, some investigators might alter sample inclusion criteria after data are collected, which could increase the likelihood of finding a positive effect. In cancer prognostic studies, it was found that inconsistent reporting of patient outcomes was likely to introduce bias in study findings that could spuriously inflate the significance of prognostic factors (Kyzas et al., 2005). Bias can be inferred by the number of published studies with p-values that irregularly cluster around the “p < 0.05” value (Head et al., 2015). Many scholars have advocated for greater prespecification of study designs in both observational and controlled trials to reduce the likelihood that study design can be manipulated to achieve positive results (Head et al., 2015). Recently, more than 800 researchers from more than 50 countries also proposed abandoning the use of statistical significance to decide whether a result refutes or supports a scientific hypothesis (Amrhein et al., 2019).

Reproducibility problems arise in several subfields relating to cancer control for different reasons, perhaps notably because of the sheer biological complexity of the system under analysis. A 2012 Nature editorial argued that success in oncology drug development has been limited by unreliable results from preclinical studies, with reference to a report that Amgen scientists were only able to replicate 11 percent of study findings from 53 landmark studies in hematology and oncology (Begley and Ellis, 2012). This lack of study replication may be due in part to inadequate descriptions of the experimental methods and variability in techniques or cell line and mouse models, but regardless of the cause, the implications are significant. Translating preclinical findings to human trials, which often focus on survival as an end point, requires a substantial investment of resources and time. Thus, accurate and reliable preclinical results are critical for advancing progress in the field.

Challenges with the reproducibility of study findings also arise in fields that rely on the mining of large, observational data sets. For example, nutritional epidemiology studies often make the headlines for identifying associations between dietary intake and cancer risk, but the results from different studies may be contradictory. Coffee, as one example, has been reported to either increase or reduce the risks of cancers—and Parkinson’s disease—depending on the study (Carroll, 2015). The results also vary depending on the populations studied, how the exposure and end points are assessed, and what statistical tools were used. A systematic review of studies that sampled 50 ingredients commonly listed in cookbooks found that 80 percent of these ingredients had been studied in relation to risk of cancer, with 39 percent of the studies reporting increased risk, 33 percent reporting decreased risk, and 23 percent showing no evidence of either increased or decreased risk (Schoenfeld and Ioannidis, 2012).

As these examples illustrate, it is difficult to document, verify, and accurately communicate information to the public and policy makers about cancer risk factors and interventions. Public confidence in and, ultimately, public support for research on cancer control—from epidemiology to economics—could be compromised by the dissemination of poor-quality evidence.

Moreover, recent media headlines highlight three new developments in cancer care and research that also have the potential to influence public trust. First is the increased and questionable promotion of services directly to patients by some medical centers and the rapidly growing marketing expenditures of drugs by biopharmaceutical companies (see Box 2-6 for additional discussion on promotion of cancer services and products). The second development is the lack of full disclosure by some researchers of financial ties to for-profit companies and other interested parties. Recent news reports have centered on medical leaders (including a chief executive officer and a chief medical officer of a renowned cancer center and a dean of a prominent medical school) who failed to disclose their financial relationships with biopharmaceutical and medical businesses in multiple publications (Ornstein and Thomas, 2018). This does not necessarily mean that the results from their published research are inaccurate, but the lack of responsible disclosure—a long-standing concern in biomedical and related research—could adversely influence public trust in cancer research. The third development is violation of anti-kickback laws by drug manufacturers, highlighted by a case in which one drug manufacturer effectively used donations and patient advocacy groups to subsidize drug costs for patients enrolled in Medicare (Thomas, 2018). Federal anti-kickback laws prohibit this practice.

TOWARD A CONSOLIDATED VISION

What can be seen from this chapter’s brief overview is that the cancer control system—in the United States but also in the rest of the world—is a collection of many individual components, only minimally integrated, that has been built up over time with little overarching vision or strategy and yielding varied results. However, despite the vital importance of cancer control in terms of both its financial and social costs, no one has yet applied a systems approach to the cancer control system in any comprehensive way.

As described in the next chapter, there have been efforts to understand certain individual components of the cancer control system—tobacco control and survivorship, for instance—with systems analysis, but those cannot answer questions about the entire cancer control system. For example, there has never been a serious attempt to analyze prevention and

treatment efforts as part of the same interconnected system and to determine what combination of prevention and treatment strategies will have the greatest benefit for a given cost. Doing so will require a completely different approach to better understanding and shaping a system using the approaches and tools of systems engineering.

FINDINGS

Finding 2-1: Historically, national strategic plans have been successfully established and refined to meet the prioritized needs of population health, national security, transportation, and economic development over the past century. However, the development of an overarching, unified national strategic vision for cancer control in the United States has been particularly impeded by the sheer

variety of participants and their programmatic, financial, professional, and other motivations.

Finding 2-2: In the United States, various initiatives pertaining to cancer control involve the leadership of at least a dozen federal government agencies in addition to those principally focused on health promotion, disease control, and medical benefits.

Finding 2-3: Cancer control activities in the United States involve hundreds of participant groups with diverse interests. Among these, as a few examples, are biopharmaceutical firms engaged in research and product development efforts, numerous professional societies setting clinical guidelines, and nonprofit patient and research advocates and individual activists.

Finding 2-4: Currently, there are at least 65 known strategic plans for cancer control across states, tribes, and territories in the United States. These contextual plans lack an integrated framework, each involving different review processes, outcomes analyses, and reporting requirements.

Finding 2-5: Currently, each state sets its own objectives and indicates how these goals were derived. Moreover, there are no criteria for what constitutes an adequate state cancer control plan.

Finding 2-6: At all levels of cancer control planning in the United States, currently no widely agreed-upon systematic standards and procedures exist to enable comprehensive performance reviews of programs and interventions, interactive monitoring of trends, and joint action for contingencies.

Finding 2-7: The current cancer control system does not provide sufficient transparency to enable a clear understanding of the potential financial influences and conflict of interests between participants such as researchers, clinicians, drug, device, and other product manufacturers as well as patient advocates and their organizations. Although a long-recognized concern, lack of public reporting of these financial relationships could continue to compromise the integrity of efforts and affect the progress in cancer control.

Finding 2-8: The current trends in the production and dissemination of information through interest groups and new forms of media and social channels—including direct marketing and advertising of products and services—can lead to a profusion of conflicting and confusing messages for patients seeking pertinent information. Promotional messages using questionable tactics to hype the benefits of their products or services run the risk of misleading patients.

Finding 2-9: Reliable evidence is a vital prerequisite for cancer research, care, and policies and, ultimately, population health. However, it is crucial that research results and publications in biomedical, public health, social and behavioral sciences, and related areas meet the central scientific standards of reproducibility and replicability required to maintain the public confidence and support, all essential for effective cancer control.

Finding 2-10: Clinical guidelines currently issued by numerous advisory and professional organizations for cancer screening and care in the United States widely diverge from one another even for a specific cancer type. These inconsistencies may lead to adverse consequences for patients and increase the financial waste in care.

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