June 28, 2016 To: NCI Blue Ribbon Panel Members From: Daniel F. Hayes, MD, FASCO ASCO President (2016-2017) The American Society of Clinical Oncology (ASCO) is very pleased to provide ideas for how the National Cancer Institute should engage in the Obama Administration’s National Cancer Moonshot Initiative. As the national organization of more than 40,000 physicians and other healthcare professionals specializing in cancer research, treatment and prevention, ASCO is fully engaged and offers our thoughts about how NCI and the Blue Ribbon Panel should approach its work on this initiative. ASCO believes that the Moonshot Initiative requires not only innovative scientific ideas but also a fundamental transformation of the way in which we conduct cancer research. We should use the moonshot for two objectives to: 1) achieve technological advances and 2) inspire our nation’s support for a robust and sustainable cancer research program. Cloning of the human genome is a great example of an important technological accomplishment that was followed rapidly by developments such as gene expression assays, which have radically changed the approach towards patients with breast cancer, and The Cancer Genome Atlas (TCGA), which has permitted us to define the mutational spectrum of most cancers. Both of these have advanced understanding in ways that allow truly personalized cancer care with greater better precision. These kinds of advances are what should be achieved with the Moonshot. ASCO believes the Cancer Moonshot has an opportunity to leverage three new innovations in technology. All three of these have already been initiated. However, they are nascent in development, and, with further development, these promising programs will provide game-changing platforms that will alter the trajectory of cancer research. First, enhancing our access to clinical outcomes databases will help us to learn from all cancer patients throughout the cancer continuum. For example, ASCO is developing CancerLinQ, a rapid learning system that will permit participating doctors to download their digital data from electronic health records for quality control analyses in real time—and it will generate unprecedented insight into cancer treatment outcomes. This effort is a true

partnership involving robust participation by oncology practices, expertise from the technology industry leader SAP, scientists and researchers at institutions across the globe, and, of course, patients whose experience is core to our understanding. But CancerLinQ is only one project. As happened when our nation sought to travel to the moon, pursuit of one goal will lead to important if unanticipated benefits. A successful cancer moonshot will need a sustained and well-funded national cancer research system and a clinical research infrastructure that extends beyond our current National Clinical Trials Network and brings trials to patients as they are identified at the point of care. Clinical trials like ASCO’s Targeted Agent and Profiling Utilization Registry (TAPUR) Study and the NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) Trial include multiple therapeutic options and operate across all cancer types. They leverage rapid advances in tumor genomic sequencing and broadening availability of such testing to facilitate participation in studies at more sites. Third, we should use digital technology and mobile devices to enhance clinical trial participants’ reporting of outcomes. We know from many studies that patient-reported data enhances data quality and our understanding of toxicity. We should better incorporate patient-reported outcomes (PRO) tools into clinical trials and ensure that we are collecting outcomes that are meaningful to patient selection of therapy. With the rapidly escalating cost of cancer care in the U.S. and dramatic changes underway in the healthcare delivery system, it is important that we develop methods to evaluate the overall value of treatments for patients to inform clinicians. To do so requires a better definition of the patient experience through collection of PROs in drug development, surveillance systems, and routine care delivery. Finally, in his remarks at ASCO’s 2016 Annual Meeting, Vice President Biden made a passionate plea for teamwork. ASCO could not agree more. We need to reduce unproductive competition and support collaboration and we need to be sure we maintain a sustainable federal funding source that matches inflation so investigators can continue to make progress in conquering cancer. It has never been more important. In addition to these three game-changing infrastructure initiatives, ASCO also advocates for support of a number of ongoing initiatives that require sustained support so that patients with cancer have a much better chance of cure and living normal, happy, and productive lives. Our recommendations on other ongoing initiatives follow the above introductory comments.

ASCO Submissions to Cancer Moonshot – June 28, 2016

1. Population-Wide Implementation of Evidence-Based Cancer Prevention 2. Clinical Trial Accrual and the Representativeness of Research Participants 3. Research to Guide Effective Survivorship Care 4. Patient-Reported Outcomes and Additional Types of Toxicity Assessments for

Measuring Effectiveness and Harms of Cancer Treatments 5. Incorporate Real-World Evidence to Enable Learning from Every Cancer

Patient 6. Biomarker Development and Validation 7. Determine Effective Ways to Improve Processes Associated with Conducting

and Managing Clinical Trials 8. Dissemination and Implementation Research on Cancer Care Delivery

Topic 1 – Population-Wide Implementation of Evidence-Based Cancer Prevention NCI Topic Category: Implementation Sciences What is the research problem? The American Society of Clinical Oncology (www.ASCO.org) is pleased to submit this Cancer Moonshot idea. A study published in the May 2016 JAMA Oncology by researchers at Harvard Medical School found that 20 to 40 percent of cancer cases, and half of cancer deaths, could be prevented if people quit smoking, avoided heavy drinking, kept a healthy weight, and got a half hour a day of moderate exercise. Many Americans are aware that these risk factors have an influence on cancer development (especially in relation to tobacco smoking), but do not implement these lifestyle changes. In addition, the aging of the U.S. population puts our country at greater risk for increased cancer incidence. These factors make it extremely important that the Cancer Moonshot invest in, develop, and implement methods to encourage population-wide implementation of evidence-based prevention methods. What is the proposed solution? The research should explore not only individual behavioral strategies, but also the socioeconomic factors that influence population health behaviors and effective approaches to implement and sustain policy and programmatic changes. For example, new technologies have emerged which can temporally and geographically monitor the impact of access to tobacco products for subjects participating in smoking cessation programs. NCI has been a prominent funder of tobacco control and cessation research. This funding opportunity should expand beyond that to include test entirely new approaches to cancer prevention and behavioral health. The research should also be required to examine sub-populations, particularly groups that are under-represented in clinical trials, e.g., racial and ethnic minorities, elderly patients, etc. How will the solution make a difference? Research findings will help inform people about effective ways to implement lifestyle changes, as well as inform public health policies and programmatic approaches. This

research also has tremendous health benefits beyond preventing cancer. It will also have a positive influence on other medical areas, including heart disease, diabetes, arthritis, etc. Reference(s)/Supporting Documentation Song M & Giovannucci E. Preventable Incidence and Mortality of Carcinoma Associated With Lifestyle Factors Among White Adults in the United States. AMA Oncol. 2015;1(4):505-527. doi:10.1001/jamaoncol.2015.0735. Tobacco Cessation & Control a Decade Later: American Society of Clinical Oncology Policy Statement Update (JCO, 2013) Topic 2 – Clinical Trial Accrual and the Representativeness of Research Participants NCI Topic Category: Expanding Clinical Trials What is the research problem? There are many barriers to patients’ participation in trials. Structural barriers affect patients’ access to clinical trials and include problems with transportation, child care, coverage of routine patient care costs, and geography (e.g., rural patients). Clinical barriers, such as unduly stringent eligibility criteria, prevent certain patients from qualifying for clinical trials. In addition, physician and patient attitudes can prevent patients who are otherwise able to participate in trials from choosing research as a treatment option. Logistical barriers that affect patient ascertainment at point of care are also critical. As a result of these barriers, there are disparities in patients’ participation in clinical trials based on (1) race and ethnicity, (2) age (both younger and older adults), (3) income, (4) education, (5) geography, and (6) gender. Moreover, less than 5% of adults diagnosed with cancer participate in clinical trials overall which dramatically slows the pace of learning and progress. Older patients are a particular challenge because they make up 60% of those with cancer and 70% of cancer deaths. Cancer incidence is increasing in older patients at a rate much higher than in those without cancer. Older patients often have other medical problems, disability, and geriatric syndromes that put them at high risk of adverse events from cancer and its treatment. Despite the unique challenges, inadequate focus has been expended by researchers, regulatory officials, and policymakers regarding enrollment of older adults on clinical trials. Furthermore, there is great heterogeneity in the aging process which necessitates individualized decision-making taking into consideration of an individual’s “functional” age. Factors captured by a geriatric assessment (e.g., functional status, comorbid medical conditions, psychological state, cognitive function, nutrition status, and social support) provide insight into an individual’s “functional” age in comparison to their “chronological age,” but are often not captured in clinical trials. Patients at the other extreme of the age spectrum, younger patients with cancer, also represent a particular challenge especially with regard to opportunities to participate in early phase clinical trials of novel agents. Adolescent and young adults with certain adult types of malignancy could be included on adult clinical trials by lowering the minimum age

for enrollment because metabolism and excretion of investigational agents in these patients is similar to or the same as that seen in adults. Where growth and development could be adversely impacted based on pre-clinical or early clinical data, a more restrictive age cut-off may be appropriate. What is the proposed solution? NCI, extramural investigators, and corporate sponsors should ensure that eligibility criteria for clinical trials are broadened and rationalized so as to allow greater participation by more diverse patient populations. Research funds should come with the requirement that investigators provide a scientific and safety rationale for each eligibility criteria included in a clinical trial. NCI should fund research to define why certain groups are underrepresented in cancer research and to evaluate and promote effective strategies for addressing these underlying causes. The NCI should support studies that use broader eligibility criteria to evaluate the safety and efficacy of cancer treatments in populations not typically represented in clinical trials. ASCO’s Targeted Agent and Profiling Utilization Registry (TAPUR) Study has attempted to do this by incorporating broader eligibility criteria to enable broader participation of patients who are more reflective of cancer patients overall. TAPUR evaluates molecularly targeted cancer drugs and collects data on clinical outcomes to learn about additional uses of these drugs outside of indications already approved by the FDA. Research proposals could explore strategies and incentives to better sensitize and empower researchers, regulators, and policymakers to better address issues and opportunities for special populations, especially the elderly, adolescents, young adults, those with challenging socioeconomic circumstances, and under-represented racial and ethnic groups. Novel approaches utilizing electronic health records should be explored to overcome low participation rates in clinical trials among all cancer patients. For example, learning healthcare systems and database mechanisms, like CancerLinQ, could be tailored to match patient characteristics captured in the electronic health record to the inclusion/exclusion criteria for NCI-funded clinical trials. The systems could signal or prompt the clinicians and research staff to flag patients who may be eligible. In addition, exploring new ways to learn from data capture in real-world clinical experience could mean that more patients participate in research beyond routine clinical trials, perhaps through new study designs that leverage routine care. ASCO is interested in exploring new styles of prospective studies, such as registry-based clinical trials and real-world data gathered with slightly more rigor than routine care. This problem could also be significantly addressed through changes to NCI’s policies governing research:

All NCI-funded research should implement specific strategies (identified by research sites) to engage patients who are underrepresented in trials in order to enroll a population that mirrors the age distribution and health risk profile of patients’

cancer type under investigation. In order to help support the requirement to implement additional efforts, the NCI should provide supplemental funding to support implementation of evidence-based strategies and development and testing of novel strategies for recruitment of under-represented populations in clinical trials. NCI previously provided supplemental funds through the Minority Initiative Program. This could be reinstated and enhanced to cover all under-represented populations.

NCI should mandate researchers identify specific scientific objectives to justify inclusion and exclusion criteria used in NCI-funded clinical trials. If the criteria do not relate to the scientific objectives or to key safety considerations, they should not be included. For example, clinical trials involving adults should allow participation of children under the age of 18, as safety considerations permit. In addition, well-managed comorbid illnesses should not prohibit enrollment on clinical trials, except where drug-drug interactions are possible or specific safety considerations have been previously documented.

NCI should work with the Centers for Medicare and Medicaid Services (CMS) to facilitate participation of the Medicare and Medicaid populations in NCI-funded cancer clinical research. For example, NCI could work with CMS and other stakeholders to identify trials that could be facilitated by coverage with evidence development to cover the off-label use of marketed drugs and other new technologies. We congratulate NCI for initiating a centralized coverage analysis process for select National Clinical Trials Network trials. ASCO was pleased to collaborate with NCI on a symposium that helped to inform and facilitate that process. We encourage NCI to share its coverage analysis information with private payers and the broader research community to help them develop centralized processes and reduce associated time and cost burdens for research sites.

How will the solution make a difference?

Enrollment of a broader population on clinical trials and gathering clinically relevant data elements in clinical trials would help improve the relevance of the evidence base to patients seen in real world practice while accelerating progress. Reference(s)/Supporting Documentation

Improving the Evidence Base for Treating Older Adults With Cancer: American Society of Clinical Oncology Statement (JCO, 2015)

Modernizing Eligibility Criteria for Molecularly Driven Trials. (JCO, 2015) Topic 3 – Research to Guide Effective Survivorship Care NCI Topic Category: Other Exceptional Opportunities What is the research problem?

According to the American Cancer Society, the number of cancer survivors in the United States is expected to grow from 14.5 million in 2014 to 19 million by 2024. According to the Institute of Medicine, “New research initiatives focused on cancer patient follow-up are urgently needed to guide effective survivorship care.” Cancer care providers and people who have survived cancer lack high-quality evidence to guide decisions about ongoing cancer surveillance, long- and late-term treatment effects, and risk for subsequent cancers. In addition, delivering seamless survivorship care is often challenging in our healthcare delivery system. What is the proposed solution? The NCI should fund research to evaluate models of coordinated, interdisciplinary survivorship care in diverse communities and across systems of care so effective care can be provided. The research could test the relative effectiveness of various models (including those identified by ASCO: 1) oncology specialist care, 2) multi-disciplinary survivorship clinic, 3) disease/treatment-specific survivorship clinic, 4) general survivorship clinic, 5) consultative survivorship clinic, 6) integrative survivorship clinic, 7) shared-care of survivor, and 8) community generalist model). The research would be particularly timely if it incorporates mechanisms to monitor the effects of different treatments as new payment models that involve risk-sharing are tested by public and private payers. The models should be specific to patient populations and practitioner and institutional resources, preferences, and limitations and identify successful approaches to delivering high-quality care of people who survive cancer. The research projects should also assess the feasibility of interventions in a wide array of healthcare settings, this is particularly important given concerns about geographic access and availability of providers. How will the solution make a difference? This will expand the evidence-base required to define optimal survivor care, including the type or components of care delivered, the manner in which care is delivered and by whom, and the efficacy of the various models of care. Increased research will also improve the understanding of the late and long-term effects of cancer treatment among survivors. Reference(s)/Supporting Documentation American Cancer Society: Cancer Treatment & Survivorship Facts & Figures 2014-2015. http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-042801.pdf American Society of Clinical Oncology Statement: Achieving High-Quality Cancer Survivorship Care (JCO, 2013)

From Cancer Patient to Cancer Survivor: Lost in Transition. Institute of Medicine (2005) Topic 4 – Patient-Reported Outcomes for Measuring Effectiveness and Harms of Cancer Treatments

NCI Topic Category: Other Exceptional Opportunities What is the research problem? People with cancer frequently experience symptoms and physical function impairment – both from the cancer itself and from treatment adverse effects. Defining how people feel and function is a cornerstone of both cancer research and care delivery. The gold standard for collecting this information is measurement of “patient-reported outcomes (PROs)” – essentially, rigorously developed questionnaires that patients complete during and between visits. Unfortunately, this information is rarely collected either in the research setting or in routine practice. As a result, we have very limited information about the impact of treatments on patients’ lives. This missing information limits our ability to adequately assess safety and efficacy and tailor treatments to the unique needs and preferences of individuals. NCI has played an important role in advancing the field of patient-reported outcomes (PROs) in cancer clinical research. With the recent release of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), NCI has provided investigators with a more rigorous tool and the technology to incorporate PROs into clinical trials. As part of the development process, the academic and community consortium selected 78 symptomatic adverse events (AEs) that are amenable to self-reporting by people with cancer from the 790 AEs included in the CTCAE. With the rapidly escalating cost of cancer care in the U.S. and dramatic changes underway in the healthcare delivery system, it is important that we develop methods to evaluate the overall value of treatments for patients to inform clinicians. To do so requires a better definition of the patient experience through collection of PROs in drug development, surveillance systems, and routine care delivery. The PRO-CTCAE includes many of the important medical and clinical conditions patients experience, but there are other factors associated with the treatment that the patients clinicians could prioritize when making a treatment decision. ASCO is currently examining this issue in its work on developing an oncology value framework. Our efforts are compromised by the available data from clinical trials to incorporate into the framework. As stated by the ASCO Oncology Value Framework authors:

“The Task Force is well aware that there are many elements that might be important to individual patients in assessing the relative value of their treatment options that are not taken into account in our model. These include the convenience of receiving therapy, the avoidance of interrupting the flow of activities of daily living, and the impact of a treatment on quality of life (QoL) and the ability to achieve personal and professional goals. These are domains that could be measured under the broad rubric of patient-reported outcomes (PROs). Much work is needed to develop reliable assessments and consistent use of PROs, both within clinical trials and as part of routine clinical care. Future versions of the framework will recognize these when they are evidence based and thereby facilitate incorporation of PROs into the determination of the NHB of a treatment.”

What is the proposed solution? There are three immediate research areas in patient-reported outcomes that can have a substantial impact:

1) Support research to determine optimal approaches for using PRO-CTCAE in early-

phase clinical trials to determine patient-centered tolerability, dose, and schedule.

2) Support implementation research for integrating the PRO-CTCAE symptom

measure, Patient Reported Outcomes Measurement Information System (PROMIS)

physical function measure, and geriatric assessment measures into routine clinical

practice, including: interfacing with EHR systems; integrating into clinical workflow;

testing dynamic feedback models between clinicians and patients for symptom

management; and testing of patient monitoring between visits.

3) Conduct research to identify which symptoms are most important to specific cancer

populations. Limited initial work in this area was started by an NCI consensus

conference but has not gone further.

There are immediate research infrastructure development areas for patient-reported outcomes that can have a substantial impact:

1) The PRO-CTCAE for symptoms and PROMIS for physical functioning should be

included in the NCI’s SEER registry, to collect the patient experience within SEER.

2) Precision medicine and other clinical trials assessing cancer therapies should

routinely include the PRO-CTCAE for symptoms and PROMIS for physical

functioning.

3) If a trial is including the CTCAE, then it should also include the PRO-CTCAE.

4) Research should incorporate factors captured by a geriatric assessment (e.g.,

functional status, comorbid medical conditions, psychological state, cognitive

function, nutrition status, and social support) provide insight into an individual’s

“functional” age in comparison to their “chronological age,” but are often not

captured in clinical trials.

How will the solution make a difference? Work in this area will inform the research community and add to important publicly available tools – the PRO-CTCAE and PROMIS. This work will vastly increase understanding of the patient experience with cancer and its treatment, and enable true patient-centered drug development and care delivery. Ultimately, collecting patient-reported data will help clinicians in partnering with their patients in treatment decision-making. Organizations like ASCO will be able to develop educational tools and practice guidelines using this information to facilitate clinician preparation for discussions around decision-making.

ASCO is particularly interested in incorporating this kind of data into its Value Framework tools. Reference(s)/Supporting Documentation Basch E, et al. Development of the National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) J Natl Cancer Inst (2014) 106 (9): dju244 Basch E. Toward patient-centered drug development in oncology. N Engl J Med 2013;369(5):397-400. PMID: 23822654. Schnipper LE, et al. Updating the American Society of Clinical Oncology Value Framework: Revisions and Reflections in Response to Comments Received. JCO May 31, 2016, doi: 10.1200/JCO.2016.68.2518 Topic 5 – Incorporate Real-World Evidence to Enable Learning from Every Cancer Patient NCI Topic Category: Enhanced Data Sharing What is the research problem? One of the most frustrating challenges we face as clinicians is that people with cancer have complex medical conditions and other non-healthcare needs, yet almost all we know about cancer diagnosis, treatment, and prevention comes from a tiny subset of patients—the 3 to 5 percent who enroll in clinical trials, who are typically younger, fit patients. Clinical trials enroll relatively homogeneous patient populations, which leaves us with a lack of evidence to guide treatments for a large proportion of the other 95 to 97 percent who do not participate in, or do not qualify for studies. Clinical outcomes for millions of individuals with cancer are present in medical records and databases that, for the most part, do not communicate and not easily retrieved. By standardizing the real-life information on our patients—and making data from electronic health records truly interoperable— and aggregating it into a common database, we can vastly speed discovery and enable the possibility of personalized care in the future for every cancer patient. Insights that have taken years to discern could happen much more quickly, helping us to understand treatments that work, those that don’t, and high impact areas where additional research is critically needed. In addition, discoveries made possible by the Moonshot Initiative, can be returned quickly to patients and clinicians thereby democratizing data and speeding the distribution of advances. This vision is one that has been accomplished outside of medicine and ASCO is excited by the possibility that the cancer care community can accelerate learning and improve quality of care quickly using this approach. ASCO is using this approach in both CancerLinQ (Cancer Learning Intelligence Network for Quality) and the TAPUR (the Targeted Agent and Profiling Utilization Registry) study. The

primary purpose of CancerLinQ is to promote high quality care for every patient by quickly sharing and exchanging large amounts of data. Similar to the information-aggregating power of Google or Amazon, CancerLinQ will identify trends among millions of patients with almost every treatment, tumor type and genomic profile—and bring them to the attention of medical professionals who can translate them to improved patient care. The TAPUR study is prospectively evaluating molecularly targeted cancer drugs and collecting data on clinical outcomes to learn about additional uses of these drugs outside of indications already approved by the FDA. TAPUR is a study grounded in real-world clinical practice – relying on physician judgment, collecting clinical outcomes as monitored in routine practice, and enabling participation of patients who are more reflective of cancer patients overall. What is the proposed solution? Maximize federal support for research projects aimed at learning from real-world clinical data and combining data from multiple sources. The expansion of new science, treatments and diagnostic tests make big data initiatives more important than ever so that we can quickly learn how best to apply these breakthrough treatments to the diverse U.S. population. This type of research also provides important supplemental information to clinical trials data and enhances the overall evidence base, particularly where prospective trials are not possible. Federal support for research with big data will help advance the methodology, encourage collaboration, and help ensure that the results inform the entire research community. ASCO is eager to work with NCI and its funded investigators to collaborate and maximize our potential to learn from data collected in CancerLinQ and TAPUR. For example, linking the Medicare-Surveillance, Epidemiology and End Results (SEER) database to CancerLinQ will increase the reach of Medicare-SEER (currently only 28 percent of the nation’s cancer cases) and add important clinical information from physicians’ offices, where nearly 80 percent of cancer treatment occurs. Research that leverages real-world data can also improve understanding of demographics and practice patterns related to physicians, patients, and payers that drive delivery of care and outcomes, ultimately leading to interventions to improve quality of care and eliminate disparities. Cancer Big Data Laboratory - We recommend that NCI provide funding to permit organizations to partner and develop a Big Data Laboratory in which organizations (such as CI4CC and ASCO) could deposit de-identified datasets and make them available to informaticists to use for methods development. We need innovative methods for analyses of big data and our cancer center informaticists are well poised to develop and test methods and strategies. The new methods would then become available to CancerLinQ and others for analysis of other data sets. The field of big data analysis is developing at hyper speed because of the computing potential and large amounts of data that are being collected and accessible. Testing methods and strategies for analysis will require large amounts of data, and the laboratory would be a good environment in which to do it. This problem could also be significantly addressed through changes to NCI’s policies governing research:

NCI should review its list of common data elements for researchers to collect in

clinical trials to ensure that NCI-funded trials capture measures from the geriatric assessment domains (e.g., functional status, comorbid medical conditions, psychological state, cognitive function, nutrition status, and social support), socioeconomic status, and geographic demographics and should provide sufficient per-case reimbursement to capture this information.

NCI should make supplemental funding available to enable all NIH, NCI, and NCI-funded clinical databases to collect geriatric assessment, socioeconomic status, and geographic data and have the functionality to support studies designed to improve the evidence base supporting the treatment of older adults and underserved populations with cancer.

How will the solution make a difference? An NCI funding opportunity announcement focused on learning from real-world data across multiple data sources will enable NCI and its funded investigators to be leaders and standard-setters in the rapidly evolving field of big data research. It will also send a strong message to health information technology vendors that the value of the data they are collecting is maximized when it can be securely aggregated across multiple platforms. ASCO is pleased about the recent collaboration between CancerLinQ and the Cancer Informatics for Cancer Centers (CI4CC). The collaboration will bring together CancerLinQ (which has practices in a wide variety of settings throughout the U.S.) with informatics scientists and technology leaders at NCI-funded cancer centers and other academic cancer centers throughout the world. The TAPUR study also involves research sites in the community and at academic centers. Big data research would provide the potential to learn from cancer survivors about the long- and late-term effects of cancer treatment, as well as ongoing surveillance needs. Reference(s)/Supporting Documentation Topic 6 – Biomarker Development and Validation NCI Topic Category: Tumor Evolution & Progression What is the research problem? Precision medicine is predicated on the development of therapies that are targeted at the biological triggers that cause or permit cancer development and proliferation. In addition, due to recent successes, immunotherapy treatments are in the public spotlight and, many people with cancer are requesting this therapy. Unfortunately, we do not currently have enough reliable biomarkers to identify which patients are likely to benefit.

Biomarkers and other distinguishing characteristics of patients will be required to more accurately determine who will benefit from these therapies. The field of biomarker identification, testing, and validation is rapidly changing, and clinicians and researchers have limited understanding of which approaches have analytical and clinical validity and clinical utility in cancer treatment. We do not have a sufficient repertoire of proven, easily measured biomarkers to identify patients based on the molecular characteristics of their cancer, or to monitor the effectiveness of prevention and therapeutic strategies in real time. To move away from the one-size-fits-all approach to cancer therapy and effectively deliver precision medicine requires high-quality biomarkers – making the biomarker as important as the targeted therapy. New biomarkers tests are rapidly entering clinical practice, often with limited evidence of clinical utility, and both physicians and payers are uncertain about which tests should be used and which tests should be paid for. Our healthcare system does not currently provide or support mechanisms to learn about the utility of biomarker tests once they are introduced into practice. What is the proposed solution? Coverage with data development (CDD) is a coverage mechanism available to CMS and some commercial payers that allows reimbursement for new treatments and tests if data on patient outcomes are prospectively captured to help validate the utility of the intervention and the coverage decision. ASCO data collection platforms like TAPUR and CancerLinQ are available to collect the necessary data and provide it to test developers and payers in a coverage with data development program. For example, a test developer with a new genomic test might agree to participate in a CDD with CMS that allows CMS to provide reimbursement for the test if outcomes data are captured and reported. Such a test could then be used to qualify patients to participate in the TAPUR study which then collects patient data on treatment administered based on the test results and outcomes experienced by patients. TAPUR reports the results to the test developers and CMS. This type of program allows promising new tests to be implemented with guaranteed reimbursement in a setting that enables robust data capture about the performance and utility of the test. How will the solution make a difference? CDD programs for new biomarker tests will rapidly accelerate test development and market entry and enable test validation using existing data collection vehicles such as TAPUR and CancerLinQ. Test developers, patients, clinicians and payers will all benefit from programs that incentivize and support more rapid evidence development about the utility of novel biomarker tests. Reference(s)/Supporting Documentation National Academies of Sciences, Engineering, and Medicine. 2016. Biomarker tests for molecularly targeted therapies: Key to unlocking precision medicine. Hayes DF. Breaking a Vicious Cycle. Science Translational Medicine, 31 Jul 2013:Vol. 5, Issue 196, pp. 196.

Topic Area 7 – Determine Effective Ways to Improve Processes Associated with Conducting and Managing Clinical Trials NCI Topic Category: Expanding Clinical Trials What is the research problem? According to multiple ASCO surveys of the research community, research sites are overwhelmed by the administrative and regulatory requirements associated with conducting and managing clinical trials, which are impediments at various stages of the clinical trial process (i.e., getting trials up and running, during the trials, and post-trial activities and follow-up). Coalitions have developed or standardized tools and resources to try to improve some of these processes, but there has been little, if any, uptake or impact. None of these prior initiatives appear to have convened all relevant stakeholders nor has there been complete ‘buy-in’ or adoption of the tools and resources. Many cancer clinical trials are conducted with federal funds (most frequently NCI or NIH) and submitted to the Food and Drug Administration (FDA) for review. As a result, trials are required to comply with all regulatory requirements for federally sponsored trials (e.g., the Common Rule, National Institute of Health rules, FDA rules, HIPAA privacy and security rules, etc.). These differing standards make it challenging to efficiently launch clinical trials and create regulatory silos across federal agencies, compromising our ability to conduct analyses across clinical trials. One example of differing standards across agencies is reporting of adverse events. Each agency has different definitions and time requirements for reporting on safety. In addition, the reports are not submitted in a standard electronic format, so regulators are unable to easily compare safety issues for a single therapy across the hundreds of clinical trials that involve that therapy. As a result, we are awash in safety reports and do not have a meaningful way to distinguish the important safety signals from the cacophony of reports. What is the proposed solution? Policy Solutions: NCI should help launch a trans-HHS, multi-stakeholder analysis of regulatory requirements related to clinical trials and create a single, uniform standard for conducting trials that involve federal funds and/or are submitted to federal agencies for review. This initiative should include public (including the National Institutes of Health, Food and Drug Administration, Centers for Medicare and Medicaid Services, Office for Human Research Protections, Office for Civil Rights, and others) and private (including patients, community and academic investigators, trial sponsors) stakeholders in the research process and

should involve meetings with the public. The goal should be to create a uniform and standardized process for conducting publicly and privately funded clinical trials. One of the issues that the multi-stakeholder group should address is the current system of reporting adverse events in research with the goal of standardizing and consolidating reporting. The federal government should also leverage the movement toward electronic conduct of trials and submission of data by creating a single, online platform for confidentially and securely submitting required adverse event reports. Research Solutions:

NCI should fund research into methods for better disseminating existing tools and resources to help standardize the clinical trial process.

NCI should fund research to identify effective strategies for improving the efficiency of cancer clinical trials.

These tools and strategies could be related to administrative processes for conducting clinical trials, as well as regulatory science to improve the process for conducting trials for submission to federal agencies and for oversight by federal agencies. How will the solution make a difference? Improving administrative and regulatory processes will help to expedite clinical trial implementation and facilitate clinical trial participation for research sites and sponsors. Importantly, such improvements will also help to ensure patients have timely access to clinical trials and important new treatments. Developing solutions with all stakeholder groups will help to provide insight and clarity, determine feasibility, and establish agreements and ‘buy-in’ from all relevant parties, which has been a barrier to implementing potential solutions and affecting change. Standardizing regulatory requirements for conducting clinical trials will dramatically reduce the time it takes to initiate trials and improve the ability to look across clinical trials and draw meaningful conclusions. Reference(s)/Supporting Documentation Addressing Administrative and Regulatory Burden in Cancer Clinical Trials: Summary of a Stakeholder Survey and Workshop Hosted by the American Society of Clinical Oncology and the Association of American Cancer Institutes. Vose et al, manuscript in preparation, to be submitted to JCO. Challenges with Research Contract Negotiations in Community-Based Cancer Research. Thompson et al, JOP, 2016.

Topic 8 – Dissemination and Implementation Research on Cancer Care Delivery NCI Topic Category: Other Exceptional Opportunities What is the research problem? Our healthcare delivery system is in the midst of fundamental changes in several aspects, including organization, payment, expectations of patients, and provider roles. The Institute of Medicine in its 2013 report characterized the U.S. cancer care delivery as a system in crisis. “Care often is not patient-centered, many patients do not receive palliative care to manage their symptoms and side effects from treatment, and decisions about care often are not based on the latest scientific evidence.” We do not understand what enables and motivates providers to optimally implement evidence-based care and avoid tests, procedures and/or treatments when common use and clinical value are not supported by available evidence. ASCO and other organizations participated in the ABIM Foundation’s Choosing Wisely initiative to help clinicians identify and avoid wasteful or unnecessary medical tests, treatments and procedures. We want to identify optimal methods and tools to enable the most rapid uptake and dissemination of evidence-based standards of care. In addition, research into the influences on healthcare delivery can lead to interventions that will improve quality and reduce disparities in care and outcomes. What is the proposed solution? A funding opportunity announcement that would encompass the following topics:

Behavioral science regarding providers – including, but not limited to, what motivates them to implement scientific advances and quality improvement activities and participate in research; what are effective ways for providers to work in teams; and what are effective strategies and programs to prevent and mitigate burnout.

Healthcare delivery science – including, but not limited to, how are changes in the healthcare delivery system affecting delivery of quality cancer care; how could systems be organized to better promote coordinated care;

Models of care and care coordination interventions – including, but not limited to, assessment and decision-making approaches, communication interventions, electronic health record support mechanisms, as well as comparative effectiveness research all will help provide better information on how to improve care delivery for all patients, but particularly those with increased needs, such as older patients with cancer.

In this time of rapid change in the healthcare delivery system “natural experiments” could be undertaken to address these issues, leveraging administrative data in the context of policy changes that affect care delivery and payment (e.g. Affordable Care Act, Medicaid expansion, Accountable Care Organizations, novel payer arrangements, etc.).

How will the solution make a difference? The research will identify effective approaches to structure or restructure our cancer care delivery system to deliver high-quality cancer care. Reference(s)/Supporting Documentation Institute of Medicine. Delivering High-Quality Cancer Care: Charting a new course for a system in crisis. (2013).