Financial Implications of Avapritinib for Treatment of Unresectable Gastrointestinal Stromal Tumors in Patients With a PDGFRA Exon 18 Variant or After 3 Previous Therapies in a Hypothetical US Health Plan.

Importance: With the approval of avapritinib for adults with unresectable or metastatic gastrointestinal stromal tumors (GISTs) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 variant, including PDGFRA D842V variants, and National Comprehensive Cancer Network guideline recommendations as an option for patients with GIST after third-line treatment, it is important to estimate the potential financial implications of avapritinib on a payer's budget. Objective: To estimate the budget impact associated with the introduction of avapritinib to a formulary for metastatic or unresectable GISTs in patients with a PDGFRA exon 18 variant or after 3 or more previous treatments from the perspective of a US health plan. Design, Setting, and Participants: For this economic evaluation, a 3-year budget impact model was developed in March 2020, incorporating costs for drug acquisition, testing, monitoring, adverse events, and postprogression treatment. The model assumed that avapritinib introduction would be associated with increased PDGFRA testing rates from the current 49% to 69%. The health plan population was assumed to be mixed 69% commercial, 22% Medicare, and 9% Medicaid. Base case assumptions included a GIST incidence rate of 9.6 diagnoses per million people, a metastatic PDGFRA exon 18 mutation rate of 1.9%, and progression rate from first-line to fourth-line treatment of 17%. Exposures: The model compared scenarios with and without avapritinib in a formulary. Main Outcomes and Measures: Annual, total, and per member per month (PMPM) budget impact. Results: In a hypothetical 1-million member plan, fewer than 0.1 new patients with a PDGFRA exon 18 variant per year and 1.2 patients receiving fourth-line therapy per year were eligible for treatment. With avapritinib available, the total increase in costs in year 3 for all eligible adult patients with a PDGFRA exon 18 variant was $46 875, or $0.004 PMPM. For patients undergoing fourth-line treatment, the total increase in costs in year 3 was $69 182, or $0.006 PMPM. The combined total budget impact in year 3 was $115 604, or $0.010 PMPM, including an offset of $3607 in postprogression costs avoided or delayed. The higher rates of molecular testing resulted in a minimal incremental testing cost of $453 in year 3. Conclusions and Relevance: These results suggest that adoption of avapritinib as a treatment option would have a minimal budget impact to a hypothetical US health plan. This would be primarily attributable to the small eligible patient population and cost offsets from reduced or delayed postprogression costs.

Study protocol: Whole genome sequencing Implementation in standard Diagnostics for Every cancer patient (WIDE).

BACKGROUND: 'Precision oncology' can ensure the best suitable treatment at the right time by tailoring treatment towards individual patient and comprehensive tumour characteristics. In current molecular pathology, diagnostic tests which are part of the standard of care (SOC) only cover a limited part of the spectrum of genomic changes, and often are performed in an iterative way. This occurs at the expense of valuable patient time, available tissue sample, and interferes with 'first time right' treatment decisions. Whole Genome Sequencing (WGS) captures a near complete view of genomic characteristics of a tumour in a single test. Moreover, WGS facilitates faster implementation of new treatment relevant biomarkers. At present, WGS mainly has been applied in study settings, but its performance in a routine diagnostic setting remains to be evaluated. The WIDE study aims to investigate the feasibility and validity of WGS-based diagnostics in clinical practice. METHODS: 1200 consecutive patients in a single comprehensive cancer centre with (suspicion of) a metastasized solid tumour will be enrolled with the intention to analyse tumour tissue with WGS, in parallel to SOC diagnostics. Primary endpoints are (1) feasibility of implementation of WGS-based diagnostics into routine clinical care and (2) clinical validation of WGS by comparing identification of treatment-relevant variants between WGS and SOC molecular diagnostics. Secondary endpoints entail (1) added clinical value in terms of additional treatment options and (2) cost-effectiveness of WGS compared to SOC diagnostics through a Health Technology Assessment (HTA) analysis. Furthermore, the (3) perceived impact of WGS-based diagnostics on clinical decision making will be evaluated through questionnaires. The number of patients included in (experimental) therapies initiated based on SOC or WGS diagnostics will be reported with at least 3 months follow-up. The clinical efficacy is beyond the scope of WIDE. Key performance indicators will be evaluated after every 200 patients enrolled, and procedures optimized accordingly, to continuously improve the diagnostic performance of WGS in a routine clinical setting. DISCUSSION: WIDE will yield the optimal conditions under which WGS can be implemented in a routine molecular diagnostics setting and establish the position of WGS compared to SOC diagnostics in routine clinical care.

Regulatory perspectives on next-generation sequencing and complementary diagnostics in Japan.

INTRODUCTION: The 'one biomarker/one drug' scenario is unsustainable because cancer is a complex disorder that involves a number of molecular defects. In the past decade, major technological advances have lowered the overall cost and increased the efficiency of next-generation sequencing (NGS). AREAS COVERED: We review recent regulations on NGS and complementary diagnostics in Japan, mainly focusing on high-quality studies that utilized these new diagnostic modalities and were published within the last 5 years. We highlight significant changes in regulation, and explain the direction of efforts to translate the results of NGS and complementary diagnostics into clinical practice. EXPERT OPINION: NGS holds a number of advantages over conventional companion and complementary diagnostics that enable simultaneous analyzes of multiple cancer genes to detect actionable mutations. Parallel technological developments and regulatory changes have led to the rapid adoption of NGS into clinical practice. NGS-based genomic data have been leveraged to better understand the characteristics of a disease that affects its patient's response to a given therapy. As NGS-based tests become more widespread, however, Japanese authorities will face significant challenges particularly with respect to the complexity of genomic data, which will have to be managed if NGS is to benefit patients.

[Budget impact of the incorporation of GeneXpert MTB/RIF for diagnosis of pulmonary tuberculosis from the perspective of the Brazilian Unified National Health System, Brazil, 2013-2017]. / Impacto orçamentário da incorporação do GeneXpert MTB/RIF para o diagnóstico da tuberculose pulmonar na perspectiva do Sistema Único de Saúde, Brasil, 2013-2017.

The study aimed to estimate the budget impact of GeneXpert MTB/RIF for diagnosis of tuberculosis from the perspective of the Brazilian National Program for Tuberculosis Control, drawing on a static model using the epidemiological method, from 2013 to 2017. GeneXpert MTB/RIF was compared with two diagnostic sputum smear tests. The study used epidemiological, population, and cost data, exchange rates, and databases from the Brazilian Unified National Health System. Sensitivity analysis of scenarios was performed. Incorporation of GeneXpert MTB/RIF would cost BRL 147 million (roughly USD 45 million) in five years and would have an impact of 23 to 26% in the first two years and some 11% between 2015 and 2017. The results can support Brazilian and other Latin American health administrators in planning and managing the decision on incorporating the technology.

Resumo: O objetivo do estudo foi estimar o impacto orçamentário do GeneXpert MTB/RIF para o diagnóstico da tuberculose sob a perspectiva do Programa Nacional de Controle da Tuberculose, valendo-se de um modelo estático apoiado no método epidemiológico entre 2013 e 2017. Comparou-se um teste Xpert MTB/RIF com duas baciloscopias diagnósticas. Utilizaram-se dados epidemiológicos, populacionais, de custos, a taxa de câmbio e bases de dados do Sistema Único de Saúde. Foi realizada análise de sensibilidade por cenários. A incorporação do GeneXpert MTB/RIF demandaria um montante de R$ 147 milhões em cinco anos e representaria um impacto de 23% a 26% nos dois primeiros anos, e de cerca de 11% entre 2015 e 2017. Os resultados podem apoiar os gestores brasileiros e dos países latino-americanos no planejamento e gestão na sua decisão de incorporação da tecnologia.

Resumen: El objetivo del estudio fue estimar el impacto presupuestario del GeneXpert MTB/RIF para el diagnóstico de la tuberculosis, desde la perspectiva del Programa Nacional de Control de la Tuberculosis de Brasil, valiéndose de un modelo estático, apoyado en el método epidemiológico entre 2013 y 2017. Se comparó un test Xpert MTB/RIF con dos baciloscopias diagnósticas. Se utilizaron datos epidemiológicos, poblacionales, de costes, la tasa de cambio y bases de datos del Sistema Único de Salud. Se realizó un análisis de sensibilidad por escenarios. La incorporación del GeneXpert MTB/RIF demandaría un montante de R$ 147 millones en cinco años y representaría un impacto de 23 a 26% durante los dos primeros años, y de cerca de un 11% entre 2015 y 2017. Los resultados pueden apoyar a los gestores brasileiros y de los países latinoamericanos en la planificación y gestión a la hora de decidir incorporar este tipo de tecnología.

A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs.

PURPOSE: The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported. PATIENTS AND METHODS: We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system. We analyzed the outcomes of 36 patients who received genomic testing and targeted therapy (precision cancer medicine) between July 1, 2013, and January 31, 2015, compared with 36 historical control patients who received standard chemotherapy (n = 29) or best supportive care (n = 7). RESULTS: The average progression-free survival was 22.9 weeks for the precision medicine group and 12.0 weeks for the control group ( P = .002) with a hazard ratio of 0.47 (95% CI, 0.29 to 0.75) when matching on age, sex, histologic diagnosis, and previous lines of treatment. In a subset analysis of patients who received all care within the Intermountain Healthcare system (n = 44), per patient charges per week were $4,665 in the precision treatment group and $5,000 in the control group ( P = .126). CONCLUSION: These findings suggest that precision cancer medicine may improve survival for patients with refractory cancer without increasing health care costs. Although the results of this study warrant further validation, this precision medicine approach may be a viable option for patients with advanced cancer.

Impacto orçamentário da incorporação do GeneXpert MTB/RIF para o diagnóstico da tuberculose pulmonar na perspectiva do Sistema Único de Saúde, Brasil, 2013-2017 / Budget impact of the incorporation of GeneXpert MTB/RIF for diagnosis of pulmonary tuberculosis from the perspective of the Brazilian Unified National Health System, Brazil, 2013-2017 / Impacto presupuestario de la incorporación del GeneXpert MTB/RIF para el diagnóstico de la tuberculosis pulmonar desde la perspectiva del Sistema Único de Salud, Brasil, 2013-2017

Resumo: O objetivo do estudo foi estimar o impacto orçamentário do GeneXpert MTB/RIF para o diagnóstico da tuberculose sob a perspectiva do Programa Nacional de Controle da Tuberculose, valendo-se de um modelo estático apoiado no método epidemiológico entre 2013 e 2017. Comparou-se um teste Xpert MTB/RIF com duas baciloscopias diagnósticas. Utilizaram-se dados epidemiológicos, populacionais, de custos, a taxa de câmbio e bases de dados do Sistema Único de Saúde. Foi realizada análise de sensibilidade por cenários. A incorporação do GeneXpert MTB/RIF demandaria um montante de R$ 147 milhões em cinco anos e representaria um impacto de 23% a 26% nos dois primeiros anos, e de cerca de 11% entre 2015 e 2017. Os resultados podem apoiar os gestores brasileiros e dos países latino-americanos no planejamento e gestão na sua decisão de incorporação da tecnologia.

Abstract: The study aimed to estimate the budget impact of GeneXpert MTB/RIF for diagnosis of tuberculosis from the perspective of the Brazilian National Program for Tuberculosis Control, drawing on a static model using the epidemiological method, from 2013 to 2017. GeneXpert MTB/RIF was compared with two diagnostic sputum smear tests. The study used epidemiological, population, and cost data, exchange rates, and databases from the Brazilian Unified National Health System. Sensitivity analysis of scenarios was performed. Incorporation of GeneXpert MTB/RIF would cost BRL 147 million (roughly USD 45 million) in five years and would have an impact of 23 to 26% in the first two years and some 11% between 2015 and 2017. The results can support Brazilian and other Latin American health administrators in planning and managing the decision on incorporating the technology.

Resumen: El objetivo del estudio fue estimar el impacto presupuestario del GeneXpert MTB/RIF para el diagnóstico de la tuberculosis, desde la perspectiva del Programa Nacional de Control de la Tuberculosis de Brasil, valiéndose de un modelo estático, apoyado en el método epidemiológico entre 2013 y 2017. Se comparó un test Xpert MTB/RIF con dos baciloscopias diagnósticas. Se utilizaron datos epidemiológicos, poblacionales, de costes, la tasa de cambio y bases de datos del Sistema Único de Salud. Se realizó un análisis de sensibilidad por escenarios. La incorporación del GeneXpert MTB/RIF demandaría un montante de R$ 147 millones en cinco años y representaría un impacto de 23 a 26% durante los dos primeros años, y de cerca de un 11% entre 2015 y 2017. Los resultados pueden apoyar a los gestores brasileiros y de los países latinoamericanos en la planificación y gestión a la hora de decidir incorporar este tipo de tecnología.

Biopsy Procedures and Molecular Testing Utilization and Related Costs in Patients with Metastatic Lung Cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene rearrangements are key therapeutic targets for biomarker-driven treatment with an EGFR or ALK tyrosine kinase inhibitor (TKI) in patients with metastatic non-small cell lung cancer (NSCLC). To appropriately guide treatment decisions, since 2011, the National Comprehensive Cancer Network and the American Society of Clinical Oncology therefore recommend EGFR and ALK analysis in tumor samples obtained at the time of diagnosis in patients with non-squamous NSCLC. Currently, there are limited data on utilization patterns and cost of biopsy procedures and biomarker tests in patients with metastatic NSCLC who receive an EGFR or ALK TKI. OBJECTIVES: To (a) describe utilization patterns and costs associated with biopsy procedures and biomarker testing in patients with NSCLC who received erlotinib or crizotinib between 2009 and 2012 and (b) investigate the timing of these procedures relative to the erlotinib or crizotinib index date. METHODS: Adult patients with metastatic lung cancer were identified by ICD-9-CM diagnostic codes within the Truven Health Analytic MarketScan database. Patients were included in the analysis if they had an index erlotinib or crizotinib claim between January 1, 2009, and September 30, 2012 (index period) and were continuously enrolled for ≥ 12 months before the index claim. Because there is no specific ICD-9-CM diagnostic code for NSCLC, patients with metastatic lung cancer who received erlotinib or crizotinib were considered to have metastatic NSCLC. Using CPT and ICD-9-CM codes, lung biopsy procedures performed during the 24 months before or 12 months after the index claim date were identified. For every patient, biomarker testing claims for EGFR and ALK were identified using the molecular pathology stacked CPT code during the 2 months before or 1 month after the index date. The frequency of claims for biopsy procedures and biomarker testing was analyzed descriptively. The overall summary measures for biomarker testing, especially frequency of EGFR testing in patients receiving erlotinib, was also described as before and after 2011, the year when biomarker testing became part of the guidelines. Per patient and overall costs for biopsy procedures and biomarker testing were calculated from payer and patient perspectives. RESULTS: Of the 4,926 identified patients, 4,801 (97.5%) received erlotinib, and 125 (2.5%) received crizotinib. Biopsy procedure claims were identified for 3,579 (72.7%) patients, including 3,503 (73.0%) erlotinib recipients and 76 (60.8%) crizotinib recipients. Biomarker testing claims were identified for 675 (13.7%) patients, including 634 (13.2%) erlotinib recipients and 41 (32.8%) crizotinib recipients. Overall, most biomarker testing procedures (476 of 741) were identified in 435 (of 675) patients after year 2011. Also, among erlotinib recipients, percentage of patients receiving EGFR testing was increased over the index period. Per patient mean (SD) numbers of biopsy procedures and biomarker tests were 1.2 (1.1) and 0.2 (0.4), respectively. In the outpatient setting, per patient mean (SD) cost per biopsy procedure was $1,223 ($1,899) from the payer perspective and $60 ($147) from the patient perspective, whereas in the inpatient setting, it was $8,163 ($18,712) and $180 ($691), respectively. Among patients receiving at least 1 biomarker test, the per patient mean (SD) cost for the overall population was $891 ($1,062) and $43 ($229); for erlotinib recipients, it was $906 ($1,084) and $42 ($228); and for crizotinib recipients, it was $664 ($576) and $55 ($243) in payer and patient perspectives, respectively. CONCLUSIONS: This study provides insight into the use and cost of biopsy and biomarker testing procedures in patients with metastatic NSCLC. The low frequency of biomarker testing highlights the need for more awareness of testing to guide treatment decisions in these patients. Costs associated with biopsy procedures and biomarker testing provide insight into the economic impact on metastatic NSCLC patients treated with targeted therapy. DISCLOSURES: This study was sponsored by Merck & Co. Shinde is a study manager working for Merck under contract with AllSourcePPS, an Agile 1 company in Huntington Beach, California. Cao and Kothari are employees of Merck & Co., Kenilworth, New Jersey. Study concept and design were contributed primarily by Shinde and Kothari. Data analysis was performed by Cao. Data interpretation was performed by Shinde, Cao, and Kothari. Shinde wrote the manuscript with assistance from Cao and Kothari. The revision was completed primarily by Shinde and Kothari.

The Health Technology Assessment of companion diagnostics: experience of NICE.

Companion diagnostics are used to aid clinical decision making to identify patients who are most likely to respond to treatment. They are becoming increasingly important as more new pharmaceuticals receive licensed indications that require the use of a companion diagnostic to identify the appropriate patient subgroup for treatment. These pharmaceuticals have proven benefit in the treatment of some cancers and other diseases, and also have potential to precisely tailor treatments to the individual in the future. However, the increasing use of companion diagnostics could place a substantial burden on health system resources to provide potentially high volumes of testing. This situation, in part, has led policy makers and Health Technology Assessment (HTA) bodies to review the policies and methods used to make reimbursement decisions for pharmaceuticals requiring companion diagnostics. The assessment of a pharmaceutical alongside the companion diagnostic used in the clinical trials may be relatively straightforward, although there are a number of challenges associated with assessing pharmaceuticals where a range of alternative companion diagnostics are available for use in routine clinical practice. The UK HTA body, the National Institute for Health and Care Excellence (NICE), has developed policy for considering companion diagnostics using its Technology Appraisal and Diagnostics Assessment Programs. Some HTA bodies in other countries have also adapted their policies and methods to accommodate the assessment of companion diagnostics. Here, we provide insight into the HTA of companion diagnostics for reimbursement decisions and how the associated challenges are being addressed, in particular by NICE. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development."

Molecular medicine: how, what, and when?

Integrating molecular medicine into clinical practice will create many challenges. But the existing genetic testing paradigm may not be the right model for introducing these new technologies.

Integrating molecular medicine into the US health-care system: opportunities, barriers, and policy challenges.

Scientific support about the concept of using molecular data for risk stratification and tailoring health-care interventions to the individual--a strategy broadly defined as molecular medicine (MM)--is accumulating. Molecular-based health-care technologies are beginning to enter clinical practice, but their use has revealed many scientific, economic, and organizational barriers to the effective delivery of targeted health care. We conducted a qualitative interview study to describe the MM landscape, with an emphasis on eliciting policy recommendations for the field from a broad range of stakeholders in MM and health care. Molecular medicine has widespread support but will require changes in how molecular-based technologies are evaluated, how health care is financed and delivered, and how clinicians and consumers are trained and prepared for its use. In particular, researchers and developers need to become active participants in a variety of clinical integration strategies to realize the promise of MM.