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Hornberger J.,Cedar Associates LLC | Hornberger J.,Stanford University | Rickert J.,Cedar Associates LLC | Dhawan R.,Johnson and Johnson | And 3 more authors.
European Journal of Haematology | Year: 2010

Objectives: To estimate the cost-effectiveness of bortezomib (BTZ) compared with dexamethasone (DEX) and lenalidomide plus dexamethasone (LEN/DEX) for the treatment of relapsed/refractory multiple myeloma in Sweden.Methods: We used partitioned survival analysis to assess survival data decomposed into three states: (i) alive before disease progression; (ii) alive after progression; and (iii) dead. The effects of treatment on time to progression and overall survival (OS) were obtained from published reports of the APEX, MM-009, and MM-010 randomized clinical trials. Costs included drug and administration costs, adverse events, treatment of relapses, and end-of-life costs. Utility estimates were derived from the literature.Results: BTZ mean OS was 57.4 months compared with 44.6 and 54.1 months for DEX and LEN/DEX, respectively. Mean lifetime direct medical costs per patient were approximately 2010 SEK 1 904 462, 1 278 854, and 2 450 588 for BTZ, DEX, and LEN/DEX, respectively. Mean incremental cost per quality-adjusted life-year of BTZ compared to DEX was 2010 SEK 902,874 (€95 073) (95% CI: 514 791, 962 416) and was dominant with respect to LEN/DEX.Conclusion: BTZ and LEN/DEX are projected to prolong survival relative to DEX. From a Swedish perspective, BTZ is cost-effective compared to DEX and LEN/DEX. © 2010 John Wiley & Sons A/S.


PubMed | Stanford University, Aurora University, The Center for Cancer and Blood Disorders and Cedar Associates LLC
Type: Journal Article | Journal: Lung cancer (Amsterdam, Netherlands) | Year: 2015

Lung cancer accounts for a significant number of new cancer cases and deaths, with the majority of patients presenting with non-small cell lung cancer (NSCLC). Although epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors are recommended as an alternative to chemotherapy for certain patients, challenges exist for clinical utilization. The objective of this analysis was to assess the outcome and economic implications of a clinically validated serum-based proteomic test to guide treatment decisions in patients with advanced NSCLC, who are EGFR-negative or status unknown, and have progressed following at least one chemotherapy regimen.This analysis was conducted from a US payer perspective. Clinical outcomes were evaluated over the lifetime of a patient, based on data from randomized trials and clinical studies. The clinical endpoints included treatment utilization, adverse events, survival, and a composite measure of length and quality of life, referred to as the quality-adjusted life year (QALY). Costs for testing, treatment, surveillance, and management of adverse events were analyzed based on publicly available costs of the related procedures. The economic endpoints were cumulative lifetime direct medical costs and cost per QALY gained.In the base case, treatment recommendation for 27.3% of the patient population changed from erlotinib to chemotherapy after using the proteomic test. Overall survival increased by 0.091 year and QALYs increased by 0.050 year. The total lifetime direct medical cost per patient decreased by $135 with test-guided treatment. The findings were robust over a wide range of variation in the input parameters.The serum-based proteomic test informed treatment selection for patients with advanced NSCLC who failed previous chemotherapy regimen(s), improving QALYs and saving costs.


Altar C.A.,Mason Inc | Hornberger J.,Cedar Associates LLC | Hornberger J.,Stanford University | Shewade A.,Cedar Associates LLC | And 3 more authors.
International Review of Psychiatry | Year: 2013

Adverse events, response failures and medication non-compliance are common in patients receiving medications for the treatment of mental illnesses. A systematic literature review assessed whether pharmacokinetic (PK) or pharmacodynamic (PD) responses to 26 commonly prescribed antipsychotic and antidepressant medications, including efficacy or side effects, are associated with nucleotide polymorphisms in eight commonly studied genes in psychiatric pharmacotherapy: CYP2D6, CYP2C19, CYP2C9, CYP1A2, CYP3A4, HTR2C, HTR2A, and SLC6A4. Of the 294 publications included in this review, 168 (57%) showed significant associations between gene variants and PK or PD outcomes. Other studies that showed no association often had insufficient control for confounding variables, such as co-medication use, or analysis of medications not substrates of the target gene. The strongest gene-outcome associations were for the PK profiles of CYP2C19 and CYP2D6 (93% and 90%, respectively), for the PD associations between HTR2C and weight gain (57%), and for SLC6A4 and clinical response (54%), with stronger SLC6A4 response associations for specific drug classes (60-83%). The preponderance of evidence supports the validity of analyzing nucleotide polymorphisms in CYP and pharmacodynamic genes to predict the metabolism, safety, or therapeutic efficacy of psychotropic medications commonly used for the treatment of depression, schizophrenia, and bipolar illness. © 2013 Institute of Psychiatry.


Hornberger J.,Cedar Associates LLC | Hornberger J.,Stanford University | Doberne J.,Cedar Associates LLC | Chien R.,Cedar Associates LLC | Chien R.,Columbia University
Genetic Testing and Molecular Biomarkers | Year: 2012

Since the late 1990s, there has been an unprecedented growth in the development of new molecular and proteomic assays for clinical decision making. Despite the thousands of tests available, a standardized, well-defined, and coherent evaluation framework for these molecular assays is still lacking. We aim to summarize the publicly available appraisal criteria and to develop a succinct and accessible set of criteria that can provide a roadmap for the appraisal of gene-based laboratory developed tests (LDTs). We conducted a systematic literature review of the available molecular diagnostic framework in PubMed MD and CINAHL and identified 91 articles on existing appraisal criteria. We provided a summary of the historical appraisal system and developed an analysis of these appraisal systems, LDT-SynFRAME, which details the major criteria for evaluating molecular diagnostics in the clinical setting. Our goal with the LDT-SynFRAME system is to promote a well-informed dialog among all the stakeholders responsible for the development, approval, reimbursement, and use of new molecular classifiers. © Copyright 2012, Mary Ann Liebert, Inc.


Badani K.,Columbia University | Thompson D.J.S.,EMMES Canada | Buerki C.,GenomeDx Biosciences | Davicioni E.,GenomeDx Biosciences | And 6 more authors.
Oncotarget | Year: 2013

Background: Only a minority of prostate cancer patients with adverse pathology and biochemical recurrence (BCR) post radical prostatectomy (RP) experience metastasis and die from prostate cancer. Improved risk prediction models using genomic information may enable clinicians to better weigh the risk of metastasis and the morbidity and costs of treatment in a clinically heterogeneous population. Purpose: We present a clinical utility study that evaluates the influence on urologist treatment recommendations for patients at risk of metastasis using a genomic-based prediction model (Decipher™). Methods: A prospective, pre-post design was used to assess urologist treatment recommendations following RP in both the adjuvant (without any evidence of PSA rise) and salvage (BCR) settings. Urologists were presented de-identified pathology reports and genomic classifier (GC) test results for 24 patients from a previously conducted GC validation study in high-risk post-RP men. Participants were fellowship trained, high-volume urologic oncologists (n=21) from 18 US institutions. Treatment recommendations for secondary therapy were made based solely on clinical information (pre-GC) and then with genomic biomarker information (post-GC). This study was approved by an independent IRB. Results: Treatment recommendations changed from pre-GC to post-GC in 43% of adjuvant, and in 53% of salvage setting case evaluations. In the adjuvant setting, urologists changed their treatment recommendations from treatment (i.e. radiation and/or hormones) to close observation post-GC in 27% of cases. For cases with low GC risk (<3% risk of metastasis), observation was recommended for 79% of the case evaluations post-GC. Consistent trends were observed in the salvage setting. Conclusion: These results indicate that urologists across a range of practice settings are likely to change treatment decisions when presented with genomic biomarker information following RP. Implementation of genomic risk stratification into routine clinical practice may better direct treatment decision-making post-RP.


Klang S.H.,Clalit Health Services | Hammerman A.,Clalit Health Services | Liebermann N.,Clalit Health Services | Efrat N.,Kaplan Medical Center | And 3 more authors.
Value in Health | Year: 2010

Objective: Oncotype DX, a 21-gene assay, was clinically validated as a predictor of 10-year recurrence-free survival and treatment response in patients with early-stage estrogen-receptor-positive, lymph-node negative breast cancer (ER+ LN- ESBC). This study determined "real-life" alteration in treatment decision and economic implications of Oncotype DX use in women with ER+ LN- ESBC. Methods: Clalit Health Services (CHS, Tel Aviv, Israel), determined the proportion of women in low, intermediate and high-risk groups in the first 368 Oncotype DX assays performed, the change of adjuvant therapy recommendation following the recurrence (RS) results from Oncotype DX use, and associated chemotherapy costs. The risk of recurrence-free survival was derived from prespecified statistical protocols of NCI-sponsored trials conducted by NSABP (B-14 and B-20). Utilities were literature based. A 3% discount rate was employed. Results: Oncotype DX altered recommendations of 40% of patients, 84% of whom were changed from hormone + chemotherapy to hormonal therapy alone. Among high-risk women, 8% switched actual treatment from hormonal therapy to hormone + chemotherapy. By reducing the chemotherapy disutility, quality-adjusted life-years (QALY) increased 0.170 years. Use of Oncotype DX costs $10,770 per QALY gained. Sensitivity analyses revealed that risk reduction in the low-risk population, the cost of adverse events, and the relative risk reduction of recurrence were the most influential variables. Conclusion: Oncotype DX resulted in net QALY gain and increased overall costs, with an incremental cost-effectiveness ratio of $10,770. For CHS, Oncotype DX represents an effective and affordable approach to favorably affect the lives of women with ESBC. © 2010, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).


Hornberger J.,Stanford University | Hornberger J.,Cedar Associates LLC | Hirth R.A.,University of Michigan
American Journal of Kidney Diseases | Year: 2012

Background: In 2011, the Medicare Improvements for Patients and Providers Act replaced the case-mix-adjusted composite payment system for Medicare outpatient dialysis facilities with a bundled end-stage renal disease prospective payment system (PPS). We assessed the economic implications for modality choice of the revised Medicare payment system. Study Design: Microeconomic analyses. Setting & Population: Patients eligible for dialysis in the United States. Model, Perspective, & Timeframe: The perspective of this analysis is that of a financial administrator of a representative dialysis center in the United States. Data were obtained from the Medicare Payment Advisory Commission, the US Renal Data System, the DOPPS (Dialysis Outcomes and Practice Patterns Study) Practice Monitor, the US Bureau of Labor Statistics, and Medicare fee schedules. Interventions: Recently implemented end-stage renal disease PPS versus the prior case-mix composite payment system. Outcomes: Medicare payment per month, center fixed and variable costs per month, net difference in revenue and variable costs (direct contribution), and net difference in revenue and total costs (operating margin). Results: The direct contribution and operating margin for in-center hemodialysis and peritoneal dialysis are expected to be positive under the new bundled PPS. For Medicare fiscal intermediaries/administrators, paid treatments for home hemodialysis vary from 3.2 to more than 4.8 per week. The direct contribution and operating margin are expected to be negative for home hemodialysis if the number of paid treatments is similar between in-center and home hemodialysis; they are almost identical when the number of paid treatments increases for home hemodialysis by approximately 1 per week. Limitations: Experience across centers and intermediaries/administrators may vary. Sensitivity analyses were conducted to assess the robustness of findings and determine which variables most influenced results. Conclusions: The new bundled PPS created a financial incentive for increased use of peritoneal dialysis. Use of home hemodialysis may be influenced by number of paid treatments per week. © 2012 National Kidney Foundation, Inc.


Kennedy J.L.,University of Toronto | Altar C.A.,Mason Inc | Taylor D.L.,University of Toronto | Degtiar I.,Cedar Associates LLC | And 2 more authors.
International Clinical Psychopharmacology | Year: 2014

Patients with schizophrenia often fail to respond to an initial course of therapy. This study systematically reviewed the societal and economic burden of treatment-resistant schizophrenia (TRS). Studies that described patients with TRS published 1996-2012 were included if they collected primary data on clinical, social, or economic outcomes. All studies were independently reviewed and extracted by at least two investigators. Sixty-five studies were identified. Almost 60% (SD 18%) of patients failed to achieve response after 23 weeks on antipsychotic drug therapy. Patients with TRS had high rates of smoking (56%), alcohol abuse (51%), substance abuse (51%), and suicide ideation (44%). The incidence of severe adverse events to treatment was 4% (SD 7%). Mean quality of life for patients who were unresponsive or intolerant to treatment was ∼20% lower than that of patients in remission. Annual costs for patients with schizophrenia are $15 500-$22 300 and are 3-11-fold higher for patients with TRS. TRS remains common and costly, despite availability of many treatment options, and contributes to a significant loss in patient quality of life. Although estimates in the literature vary greatly, TRS conservatively adds more than $34 billion in annual direct medical costs in the USA. Copyright © Lippincott Williams & Wilkins.


Scott Nystrom J.,Tufts Medical Center | Hornberger J.C.,Stanford University | Hornberger J.C.,Cedar Associates LLC | Varadhachary G.R.,University of Houston | And 6 more authors.
Oncotarget | Year: 2012

Purpose: The primary tissue-site origin in over 4% of cancers remains uncertain despite thorough clinicopathological evaluation. This study assessed the effect of a Food and Drug Administration-cleared 2,000-gene-expression-profiling (GEP) test on primary tissue-site working diagnoses and management for metastatic and poorly differentiated cancers. Methods: Clinical information was collected from physicians ordering the GEP test for patients with difficult to diagnose cancers. Endpoints included diagnostic procedures, physicians' working diagnoses and treatment recommendations before and after GEP result availability, and physician reports of the test's usefulness for clinical decision making. Patient date of death was obtained, with a minimum of one year follow-up from date of biopsy. Results: Sixty-five physicians participated in the study (n=107 patients). Before GEP, patients underwent 3.2 investigations on average (e.g., radiology, endoscopy). Ten immunohistochemistry tests were used per biopsy (SD 5.2). After GEP testing, physicians changed the primary working diagnosis for 50% of patients (95% CI: 43%,58%) and management for 65% of patients (95% CI: 58%,73%). With GEP results, the recommendation for guideline-consistent chemotherapy increased from 42% to 65% of patients, and the recommendation for non-guideline-consistent regimens declined from 28% to 13%. At last follow-up, 69 patients had died, and median survival was 14.0 months (95% CI: 10.2,18.6). Thirty-three percent of patients were alive at 2 years. Conclusion: In patients with difficult-to-diagnose cancers, GEP changed the working diagnosis and management for the majority of patients. Patients for whom the GEP test was ordered had longer median survival than that historically reported for patients enrolled in treatment trials for cancer of unknown primary. © Nystrom et al.


Hornberger J.,Stanford University | Hornberger J.,Cedar Associates LLC | Lyman G.H.,Duke University | Chien R.,Cedar Associates LLC | And 2 more authors.
Value in Health | Year: 2012

Objectives: Uncertainty exists regarding appropriate and affordable use of adjuvant chemotherapy in stage II colon cancer (T3, proficient DNA mismatch repair). This study aimed to estimate the effectiveness and costs from a US societal perspective of a multigene recurrence score (RS) assay for patients recently diagnosed with stage II colon cancer (T3, proficient DNA mismatch repair) eligible for adjuvant chemotherapy. Methods: RS was compared with guideline-recommended clinicopathological factors (tumor stage, lymph nodes examined, tumor grade, and lymphovascular invasion) by using a state-transition (Markov) lifetime model. Data were obtained from published literature, a randomized controlled trial (QUick And Simple And Reliable) of adjuvant chemotherapy, and rates of chemotherapy use from the National Cooperative Cancer Network Colon/Rectum Cancer Outcomes study. Life-years, quality-adjusted life expectancy, and lifetime costs were examined. Results: The RS is projected to reduce adjuvant chemotherapy use by 17% compared with current treatment patterns and to increase quality-adjusted life expectancy by an average of 0.035 years. Direct medical costs are expected to decrease by an average of $2971 per patient. The assay was cost saving for all subgroups of patients stratified by clinicopathologic factors. The most influential variables affecting treatment decisions were projected years of life remaining, recurrence score, and patients' disutilities associated with adjuvant chemotherapy. Conclusions: Use of the multigene RS to assess recurrence risk after surgery in stage II colon cancer (T3, proficient DNA mismatch repair) may reduce the use of adjuvant chemotherapy without decreasing quality-adjusted life expectancy and be cost saving from a societal perspective. These findings need to be validated in additional cohorts, including studies of clinical practice as assay use diffuses into nonacademic settings. © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

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