Payer reimbursement practices and incentives for improving interpretation of germline genetic testing.

Germline genetic testing for inherited cancer risk has shifted to multi-gene panel tests (MGPTs). While MGPTs detect more pathogenic variants, they also detect more variants of uncertain significance (VUSs) that increase the possibility of harms such as unnecessary surgery. Data sharing by laboratories is critical to addressing the VUS problem. However, barriers to sharing and an absence of incentives have limited laboratory contributions to the ClinVar database. Payers can play a crucial role in the expansion of knowledge and effectiveness of genetic testing. Current policies affecting MGPT reimbursement are complex and create perverse incentives. Trends in utilization and coverage for private payers and Medicare illustrate opportunities and challenges for data sharing to close knowledge gaps and improve clinical utility. Policy options include making data sharing (i) a condition of payment, and (ii) a metric of laboratory quality in payment contracts, yielding preferred coverage or enhanced reimbursement. Mandating data sharing sufficient to verify interpretations and resolve discordance among labs under Medicare and federal health programs is an option for the US Congress. Such policies can reduce the current waste of valuable data needed for precision oncology and improved patient outcomes, enabling a learning health system.

A review of economic issues for gene-targeted therapies: Value, affordability, and access.

The National Center for Advancing Translational Sciences' virtual 2021 conference on gene-targeted therapies (GTTs) encouraged multidisciplinary dialogue on a wide range of GTT topic areas. Each of three parallel working groups included social scientists and clinical scientists, and the three major sessions included a presentation on economic issues related to their focus area. These experts also coordinated their efforts across the three groups. The economics-related presentations covered three areas with some overlap: (1) value assessment, uncertainty, and dynamic efficiency; (2) affordability, pricing, and financing; and (3) evidence generation, coverage, and access. This article provides a synopsis of three presentations, some of their key recommendations, and an update on related developments in the past year. The key high-level findings are that GTTs present unique data and policy challenges, and that existing regulatory, health technology assessment, as well as payment and financing systems will need to adapt. But these adjustments can build on our existing foundation of regulatory and incentive systems for innovation, and much can be done to accelerate progress in GTTs. Given the substantial unmet medical need that exists for these oft-neglected patients suffering from rare diseases, it would be a tragedy to not leverage these exciting scientific advances in GTTs.

A research agenda to support the development and implementation of genomics-based clinical informatics tools and resources.

OBJECTIVE: The Genomic Medicine Working Group of the National Advisory Council for Human Genome Research virtually hosted its 13th genomic medicine meeting titled "Developing a Clinical Genomic Informatics Research Agenda". The meeting's goal was to articulate a research strategy to develop Genomics-based Clinical Informatics Tools and Resources (GCIT) to improve the detection, treatment, and reporting of genetic disorders in clinical settings. MATERIALS AND METHODS: Experts from government agencies, the private sector, and academia in genomic medicine and clinical informatics were invited to address the meeting's goals. Invitees were also asked to complete a survey to assess important considerations needed to develop a genomic-based clinical informatics research strategy. RESULTS: Outcomes from the meeting included identifying short-term research needs, such as designing and implementing standards-based interfaces between laboratory information systems and electronic health records, as well as long-term projects, such as identifying and addressing barriers related to the establishment and implementation of genomic data exchange systems that, in turn, the research community could help address. DISCUSSION: Discussions centered on identifying gaps and barriers that impede the use of GCIT in genomic medicine. Emergent themes from the meeting included developing an implementation science framework, defining a value proposition for all stakeholders, fostering engagement with patients and partners to develop applications under patient control, promoting the use of relevant clinical workflows in research, and lowering related barriers to regulatory processes. Another key theme was recognizing pervasive biases in data and information systems, algorithms, access, value, and knowledge repositories and identifying ways to resolve them.

Multicancer Screening Tests: Anticipating And Addressing Considerations For Payer Coverage And Patient Access.

There is a tremendous public health need to identify potentially lethal cancers at earlier stages, when there is a greater chance for improved survival. Although in the US there are currently screening recommendations for only five cancers (breast, colorectal, cervical, lung, and prostate), new tests can screen for up to fifty cancers simultaneously based on a simple blood draw. However, these multicancer screening tests (also called "liquid biopsy" tests) will also present challenges to payers because of intrinsic features of the tests and the complexity of payer coverage assessments for screening tests. We describe these considerations while also offering potential solutions that can inform payers' decision making if these tests prove to be beneficial.

Association of Breast Cancer Screening Behaviors With Stage at Breast Cancer Diagnosis and Potential for Additive Multi-Cancer Detection via Liquid Biopsy Screening: A Claims-Based Study.

PURPOSE: To evaluate mammography uptake and subsequent breast cancer diagnoses, as well as the prospect of additive cancer detection via a liquid biopsy multi-cancer early detection (MCED) screening test during a routine preventive care exam (PCE). METHODS: Patients with incident breast cancer were identified from five years of longitudinal Blue Health Intelligence® (BHI®) claims data (2014-19) and their screening mammogram and PCE utilization were characterized. Ordinal logistic regression analyses were performed to identify the association of a biennial screening mammogram with stage at diagnosis. Additional screening opportunities for breast cancer during a PCE within two years before diagnosis were identified, and the method extrapolated to all cancers, including those without recommended screening modalities. RESULTS: Claims for biennial screening mammograms and the time from screening to diagnosis were found to be predictors of breast cancer stage at diagnosis. When compared to women who received a screening mammogram proximal to their breast cancer diagnosis (0-4 months), women who were adherent to guidelines but had a longer time window from their screening mammogram to diagnosis (4-24 months) had a 87% increased odds of a later-stage (stages III or IV) breast cancer diagnosis (p-value <0.001), while women with no biennial screening mammogram had a 155% increased odds of a later-stage breast cancer diagnosis (p-value <0.001). This highlights the importance of screening in the earlier detection of breast cancer. Of incident breast cancer cases, 23% had no evidence of a screening mammogram in the two years before diagnosis. However, 49% of these women had a PCE within that time. Thus, an additional 11% of breast cancer cases could have been screened if a MCED test had been available during a PCE. Additionally, MCED tests have the potential to target up to 58% of the top 5 cancers that are the leading causes of cancer death currently without a USPSTF recommended screening modality (prostate, pancreatic, liver, lymphoma, and ovarian cancer). CONCLUSION: The study used claims data to demonstrate the association of cancer screening with cancer stage at diagnosis and demonstrates the unmet potential for a MCED screening test which could be ordered during a PCE.

Genetic testing and employer-sponsored wellness programs: An overview of current vendors, products, and practices.

BACKGROUND: Employer-sponsored corporate wellness programs have spread despite limited evidence of effectiveness in improving health or reducing costs. Some programs have offered genetic testing as a benefit to employees, but little is known about this practice. METHODS: In December 2019, we conducted a systematic Google search to identify vendors offering corporate wellness programs involving genetics. We performed qualitative content analysis of publicly available information about the vendors' products and practices disclosed on their websites. RESULTS: Fifteen vendors were identified. Details regarding genetic testing offered within wellness programs were difficult to decipher from vendors' websites, including which specific products were included. No evidence was provided to support vendor claimed improvements in employer costs, employee health, and job performance. Only half offered health and genetic counseling services. Most vendors were ambiguous regarding data sharing. Disclaimer language was included in vendors' stated risks and limitations, ostensibly to avoid oversight and liability. CONCLUSION: We found a lack of transparency among corporate wellness program vendors, underscoring challenges that stakeholders encounter when trying to assess (a) how such programs are using genetics, (b) the potential benefits of such applications, and (c) the adequacy of protections to ensure scientific evidence support any health claims and genetic nondiscrimination.

Use of Real-World Evidence in US Payer Coverage Decision-Making for Next-Generation Sequencing-Based Tests: Challenges, Opportunities, and Potential Solutions.

OBJECTIVES: Given the potential of real-world evidence (RWE) to inform understanding of the risk-benefit profile of next-generation sequencing (NGS)-based testing, we undertook a study to describe the current landscape of whether and how payers use RWE as part of their coverage decision making and potential solutions for overcoming barriers. METHODS: We performed a scoping literature review of existing RWE evidentiary frameworks for evaluating new technologies and identified barriers to clinical integration and evidence gaps for NGS. We synthesized findings as potential solutions for improving the relevance and utility of RWE for payer decision-making. RESULTS: Payers require evidence of clinical utility to inform coverage decisions, yet we found a relatively small number of published RWE studies, and these are predominately focused on oncology, pharmacogenomics, and perinatal/pediatric testing. We identified 3 categories of innovation that may help address the current undersupply of RWE studies for NGS: (1) increasing use of RWE to inform outcomes-based contracting for new technologies, (2) precision medicine initiatives that integrate clinical and genomic data and enable data sharing, and (3) Food and Drug Administration reforms to encourage the use of RWE. Potential solutions include development of data and evidence review standards, payer engagement in RWE study design, use of incentives and partnerships to lower the barriers to RWE generation, education of payers and providers concerning the use of RWE and NGS, and frameworks for conducting outcomes-based contracting for NGS. CONCLUSIONS: We provide numerous suggestions to overcome the data, methodologic, infrastructure, and policy challenges constraining greater integration of RWE in assessments of NGS.

Opportunities, resources, and techniques for implementing genomics in clinical care.

Advances in technologies for assessing genomic variation and an increasing understanding of the effects of genomic variants on health and disease are driving the transition of genomics from the research laboratory into clinical care. Genomic medicine, or the use of an individual's genomic information as part of their clinical care, is increasingly gaining acceptance in routine practice, including in assessing disease risk in individuals and their families, diagnosing rare and undiagnosed diseases, and improving drug safety and efficacy. We describe the major types and measurement tools of genomic variation that are currently of clinical importance, review approaches to interpreting genomic sequence variants, identify publicly available tools and resources for genomic test interpretation, and discuss several key barriers in using genomic information in routine clinical practice.

Characterizing the Biomedical Data-Sharing Landscape.

Advances in technologies and biomedical informatics have expanded capacity to generate and share biomedical data. With a lens on genomic data, we present a typology characterizing the data-sharing landscape in biomedical research to advance understanding of the key stakeholders and existing data-sharing practices. The typology highlights the diversity of data-sharing efforts and facilitators and reveals how novel data-sharing efforts are challenging existing norms regarding the role of individuals whom the data describe.

Hopeful and Concerned: Public Input on Building a Trustworthy Medical Information Commons.

A medical information commons (MIC) is a networked data environment utilized for research and clinical applications. At three deliberations across the U.S., we engaged 75 adults in two-day facilitated discussions on the ethical and social issues inherent to sharing data with an MIC. Deliberants made recommendations regarding opt-in consent, transparent data policies, public representation on MIC governing boards, and strict data security and privacy protection. Community engagement is critical to earning the public's trust.

Importance of Participant-Centricity and Trust for a Sustainable Medical Information Commons.

Drawing on a landscape analysis of existing data-sharing initiatives, in-depth interviews with expert stakeholders, and public deliberations with community advisory panels across the U.S., we describe features of the evolving medical information commons (MIC). We identify participant-centricity and trustworthiness as the most important features of an MIC and discuss the implications for those seeking to create a sustainable, useful, and widely available collection of linked resources for research and other purposes.

The Role of Participants in a Medical Information Commons.

Meaningful participant engagement has been identified as a key contributor to the success of efforts to share data via a "Medical Information Commons" (MIC). We present findings from expert stakeholder interviews aimed at understanding barriers to engagement and the appropriate role of MIC participants. Although most interviewees supported engagement, they distinguished between individual versus collective forms. They also noted challenges including representation and perceived inefficiency, prompting reflection on political aspects of engagement and efficiency concerns.

Methodological Issues in Assessing the Economic Value of Next-Generation Sequencing Tests: Many Challenges and Not Enough Solutions.

BACKGROUND: Clinical use of next-generation sequencing (NGS) tests has been increasing, but few studies have examined their economic value. Several studies have noted that there are methodological challenges to conducting economic evaluations of NGS tests. OBJECTIVE: Our objective was to examine key methodological challenges for conducting economic evaluations of NGS tests, prioritize these challenges for future research, and identify how studies have attempted solutions to address these challenges. METHODS: We identified challenges for economic evaluations of NGS tests using prior literature and expert judgment of the co-authors. We used a modified Delphi assessment to prioritize challenges, based on importance and probability of resolution. Using a structured literature review and article extraction we then assessed whether published economic evaluations had addressed these challenges. RESULTS: We identified 11 challenges for conducting economic evaluations of NGS tests. The experts identified three challenges as the top priorities for future research: complex model structure, timeframe, and type of analysis and comparators used. Of the 15 published studies included in our literature review, four studies described specific solutions relevant to five of the 11 identified challenges. CONCLUSIONS: Major methodological challenges to economic evaluations of NGS tests remain to be addressed. Our results can be used to guide future research and inform decision-makers on how to prioritize research on the economic assessment of NGS tests.

Genetic Test Availability And Spending: Where Are We Now? Where Are We Going?

Genetic testing and spending on that testing have grown rapidly since the mapping of the human genome in 2003. However, it is not widely known how many tests there are, how they are used, and how they are paid for. Little evidence from large data sets about their use has emerged. We shed light on the issue of genetic testing by providing an overview of the testing landscape. We examined test availability and spending for the full spectrum of genetic tests, using unique data sources on test availability and commercial payer spending for privately insured populations, focusing particularly on tests measuring multiple genes in the period 2014-17. We found that there were approximately 75,000 genetic tests on the market, with about ten new tests entering the market daily. Prenatal tests accounted for the highest percentage of spending on genetic tests, and spending on hereditary cancer tests accounted for the second-highest. Our results provide insights for those interested in assessing genetic testing markets, test usage, and health policy implications, including current debates over the most appropriate regulatory and payer coverage mechanisms.

A New Framework for Patient Engagement in Cancer Clinical Trials Cooperative Group Studies.

For the past two decades, the National Cancer Institute (NCI) has supported the involvement of patient advocates in both internal advisory activities and funded research projects to provide a patient perspective. Implementation of the inclusion of patient advocates has varied considerably, with inconsistent involvement of patient advocates in key phases of research such as concept development. Despite this, there is agreement that patient advocates have improved the patient focus of many cancer research studies. This commentary describes our experience designing and pilot testing a new framework for patient engagement at SWOG, one of the largest cancer clinical trial network groups in the United States and one of the four adult groups in the NCI's National Clinical Trials Network (NCTN). Our goal is to provide a roadmap for other clinical trial groups that are interested in bringing the patient voice more directly into clinical trial conception and development. We developed a structured process to engage patient advocates more effectively in the development of cancer clinical trials and piloted the process in four SWOG research committees, including implementation of a new Patient Advocate Executive Review Form that systematically captures patient advocates' input at the concept stage. Based on the positive feedback to our approach, we are now developing training and evaluation metrics to support meaningful and consistent patient engagement across the SWOG clinical trial life cycle. Ultimately, the benefits of more patient-centered cancer trials will be measured in the usefulness, relevance, and speed of study results to patients, caregivers, and clinicians.