The Value of Targeted Therapies in Lung Cancer

The goal of this dissertation was to examine the realized value of targeted therapies in routine care and to identify opportunities for improving the return on medical spending for these technologies. Chapter 1 investigated the value of targeted therapies in lung cancer patients who were treated in routine care. This observational, claims-based analysis used propensity score, and instrumental variable methods, combined with a Kaplan Meier Sample Average estimator to calculate lifetime costs and life expectancy. An incremental comparison showed that the realized value of targeted therapies in routine care was unfavorable relative to chemotherapy treatment. Subgroup analyses revealed that initial erlotinib therapy yielded effectiveness results that are substantially lower than efficacy survival outcomes in molecularly guided trials. Our results indicated that in routine care, chemotherapy was the most cost effective strategy. The unexpectedly low outcomes with first-line erlotinib suggested that some of the value of this treatment was not being realized in practice. Chapter 2 examined the practice patterns of targeted therapies and utilization of predictive biomarker testing in routine care to better understand the observed gaps between trial-based and `real-world' outcomes with these agents. In our nationally representative cohort of lung cancer patients, we found that the vast majority of patients did not undergo molecular testing to inform first-line therapy. Our prediction models for biomarker screening and first-line treatment suggested that phenotypic enrichment criteria guided selection for testing and initiation of erlotinib therapy. Since clinical characteristics do not adequately discriminate between mutation positive and wild type tumors, these practices signal the need for wider dissemination of biomarker screening to accurately target patients towards improving therapeutic gains with erlotinib. Chapter 3 assessed the cost-effectiveness of multiplexed predictive biomarker screening to inform treatment decisions in lung cancer patients. Using a micro-simulation model to evaluate the incremental value of molecularly guided therapy compared to chemotherapy in unselected patients, we found that personalized therapy is a cost effective strategy. Our results indicated that better value of targeted therapies in lung cancer is achievable through molecularly guided treatment

Lung cancer treatment costs, including patient responsibility, by disease stage and treatment modality, 1992 to 2003

AbstractObjectivesThe objective of this analysis was to estimate costs for lung cancer care and evaluate trends in the share of treatment costs that are the responsibility of Medicare beneficiaries.MethodsThe Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 1991–2003 for 60,231 patients with lung cancer were used to estimate monthly and patient-liability costs for clinical phases of lung cancer (prediagnosis, staging, initial, continuing, and terminal), stratified by treatment, stage, and non-small- versus small-cell lung cancer. Lung cancer-attributable costs were estimated by subtracting each patient's own prediagnosis costs. Costs were estimated as the sum of Medicare reimbursements (payments from Medicare to the service provider), co-insurance reimbursements, and patient-liability costs (deductibles and “co-payments” that are the patient's responsibility). Costs and patient-liability costs were fit with regression models to compare trends by calendar year, adjusting for age at diagnosis.ResultsThe monthly treatment costs for a 72-year-old patient, diagnosed with lung cancer in 2000, in the first 6 months ranged from $2687 (no active treatment) to$9360 (chemo-radiotherapy); costs varied by stage at diagnosis and histologic type. Patient liability represented up to 21.6% of care costs and increased over the period 1992–2003 for most stage and treatment categories, even when care costs decreased or remained unchanged. The greatest monthly patient liability was incurred by chemo-radiotherapy patients, which ranged from $1617 to$2004 per month across cancer stages.ConclusionsCosts for lung cancer care are substantial, and Medicare is paying a smaller proportion of the total cost over time

TECHNOLOGY-BASED FDI, MANUFACTURING OUTPUT AND ECONOMIC GROWTH: A COMPARATIVE ANALYSIS BETWEEN NIGERIA AND MALAYSIA

The inflow of technology-based FDI into a country helps to develop the manufacturing sector which brings about an increase in aggregate output which boosts economic growth. It is against this backdrop that this study examined the link between technology-based FDI, manufacturing output and economic growth in Nigeria and Malaysia, using the Vector Autoregression (VAR) model, pointing out the lessons Nigeria can learn from the Malaysian economy. The secondary data used in this study was obtained from the World Bank and the United Nations Conference on Trade and Development (UNCTAD) spanning between 1980 and 2017. The result from this study showed that Malaysia’s FDI inflows are directed towards the manufacturing sector than the Nigerian economy, and this explains why the Malaysian manufacturing sector is more developed than that of Nigeria. Therefore, the study recommended that Nigeria should direct FDI to the manufacturing sector, as this will boost the growth rate of the economy

Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting

Substantial improvements in survival have been seen in multiple myeloma (MM) over recent years, associated with the introduction and widespread use of multiple novel agents and regimens, as well as the emerging treatment paradigm of continuous or long-term therapy. However, these therapies and approaches may have limitations in the community setting, associated with toxicity burden, patient burden, and other factors including cost. Consequently, despite improvements in efficacy in the rigorously controlled clinical trials setting, the same results are not always achieved in real-world practice. Furthermore, the large number of different treatment options and regimens under investigation in various MM settings precludes the feasibility of obtaining head-to-head clinical trial data, and there is a temptation to use cross-trial comparisons to evaluate data across regimens. However, multiple aspects, including patient-related, disease-related, and treatment-related factors, can influence clinical trial outcomes and lead to differences between studies that may confound direct comparisons between data. In this review, we explore the various factors requiring attention when evaluating clinical trial data across available agents/regimens, as well as other considerations that may impact the translation of these findings into everyday MM management. We also investigate discrepancies between clinical trial efficacy and real-world effectiveness through a literature review of non-clinical trial data in relapsed/ refractory MM on novel agent−based regimens and evaluate these data in the context of phase 3 trial results for recently approved and commonly used regimens. We thereby demonstrate the complexity of interpreting data across clinical studies in MM, as well as between clinical studies and routine-care analyses, with the aim to help clinicians consider all the necessary issues when tailoring individual patients’ treatment approaches

Good Research Practices for Measuring Drug Costs in Cost-Effectiveness Analyses: Medicare, Medicaid and Other US Government Payers Perspectives: The ISPOR Drug Cost Task Force Report—Part IV

Objectives Public programs finance a large share of the US pharmaceutical expenditures. To date, there are not guidelines for estimating the cost of drugs financed by US public programs. The objective of this study was to provide standards for estimating the cost of drugs financed by US public programs for utilization in pharmacoeconomic evaluations. Methods This report was prepared by the ISPOR Task Force on Good Research Practices—Use of Drug Costs for Cost-Effectiveness Analysis Medicare, Medicaid, and other US Government Payers Subgroup. The Subgroup was convened to assess the methodological and practical issues confronted by researchers when estimating the cost of drugs financed by US public programs, and to propose standards for more transparent, accurate and consistent costing methods. Results The Subgroup proposed these recommendations: 1) researchers must consider regulation requirements that affect the drug cost paid by public programs; 2) drug cost must represent the actual acquisition cost, incorporating any rebates or discounts; 3) transparency with respect to cost inputs must be ensured; 4) inclusion of the public program\u27s perspective is recommended; 5) high cost drugs require special attention, particularly when drugs represent a significant proportion of health-care expenditures for a specific disease; and 6) because of variations across public programs, sensitivity analyses for actual acquisition cost, real-world adherence, and generics availability are warranted. Specific recommendations also were proposed for the Medicare and Medicaid programs. Conclusions As pharmacoeconomic evaluations for coverage decisions made by US public programs grows, the need for precise and consistent estimation of drug costs is warranted. Application of the proposed recommendations will allow researchers to include accurate and unbiased cost estimates in pharmacoeconomic evaluations

INSIGHT MM: a large, global, prospective, non-interventional, real-world study of patients with multiple myeloma

With the introduction of new drugs with different mechanisms of action, multiple myeloma (MM) patients’ outcomes have improved. However, the efficacy seen in clinical trials is often not seen in real-world settings and data on the effectiveness of MM therapies are needed. INSIGHT MM is a prospective, global, non-interventional, observational study that is enrolling approximately 4200 patients with newly diagnosed or relapsed/refractory MM, making it the largest study of its kind to date. The study aims to describe contemporary, real-world patterns of patient characteristics, clinical disease presentation, therapies chosen, clinical outcomes (response, treatment duration, time-to-next-therapy, progression-free and overall survival), safety, healthcare resource utilization and quality of life. One interim analysis has been conducted to date; current accrual is approximately 3094 patients

Network meta-analysis for indirect comparison of lanadelumab and berotralstat for the treatment of hereditary angioedema

Aim: With no head-to-head studies comparing the effectiveness of lanadelumab and berotralstat for prevention of hereditary angioedema (HAE) attacks, this networkmeta-analysis (NMA) aimed to indirectly compare the effectiveness of these treatments. Materials & methods: The NMA, using the published data from Phase III trials, was performed using a frequentist weighted regression-based approach following Ru¨ cker et al. Efficacy outcomes of interest were HAE attack rate per 28 days and ≥90% reduction in monthly HAE attacks. Results & conclusion: In this NMA, lanadelumab 300 mg administered every 2 weeks or every 4 weeks was associated with statistically significantly higher effectiveness versus berotralstat 150 mg once daily (q.d.) or 110 mg q.d. for both efficacy outcomes assessed

Global epidemiology of amyloid light-chain amyloidosis

Abstract Background Amyloid light-chain (AL) amyloidosis is an ultra-rare disease associated with significant morbidity and mortality. Few studies have examined the global epidemiology of this condition. Methods This study estimated the diagnosed incidence and 1-year, 5-year, 10-year, and 20-year period prevalence of AL amyloidosis in 2018 for countries in and near Europe, and in the United States (US), Canada, Brazil, Japan, South Korea, Taiwan, and Russia. A systematic literature review (SLR) was conducted to identify country-specific, age- and gender-specific diagnosed incidence of AL amyloidosis and observed survival data-point inputs for an incidence-to-prevalence model. Extrapolations were used to estimate incidence and prevalence for countries without registry or published epidemiological data. Results Of 171 publications identified in the SLR, 10 records met the criteria for data extraction, and two records were included in the final incidence-to-prevalence model. In 2018, an estimated 74,000 AL amyloidosis cases worldwide were diagnosed during the preceding 20 years. The estimated incidence and 20-year prevalence rates were 10 and 51 cases per million population, respectively. Conclusions Orphan medicinal product designation criteria of the European Medicines Agency or Electronic Code of Federal Regulations indicate that a disease must not affect > 5 in 10,000 people across the European Union or affect < 200,000 people in the US. This study provides up-to-date epidemiological patterns of AL amyloidosis, which is vital for understanding the burden of the disease, increasing awareness, and to further research and treatment options

Health-related quality of life is maintained with ixazomib maintenance in post-transplant newly diagnosed multiple myeloma: the TOURMALINE-MM3 trial

Objectives: Health-related quality of life (HRQoL) is particularly important during maintenance therapy (MT) in newly diagnosed multiple myeloma post-transplant, when disease symptoms are limited. Methods: We assessed HRQoL in patients randomised to 26 cycles of MT (ixazomib vs placebo) in TOURMALINE-MM3 (NCT02181413). Results: The characteristics at study entry were well-balanced between ixazomib (n = 386) and placebo (n = 251) arms. At study entry, EORTC QLQ-C30 and MY20 scores were high for functional scales and low for symptom scales and were comparable with those of the general population. Changes in subscale scores across intervals, analysed over 30 four-week intervals using a linear mixed-effects model, were generally small and similar between arms for the EORTC QLQ-C30 Global Health Status/QoL, Physical Functioning, and Pain subscales and EORTC QLQ-MY20 Disease Symptoms subscale and Peripheral Neuropathy item. EORTC QLQ-C30 Nausea/Vomiting and Diarrhoea subscales were consistently worse for ixazomib than for placebo, in line with the ixazomib toxicity profile. Even when least-squares mean differences between arms were statistically significant, none reached the established minimal important clinical difference of 10 in multiple myeloma. Conclusions: In addition to improvement in progression-free survival with ixazomib, HRQoL was maintained in both arms. Active treatment with ixazomib did not have an adverse impact on HRQoL. © 2019 Takeda Pharmaceuticals. European Journal of Haematology published by John Wiley &amp; Sons Lt