Josh J. Carlson

Linking payment to health outcomes: A taxonomy and examination of performance-based reimbursement schemes between healthcare payers and manufacturers

OBJECTIVE To identify, categorize and examine performance-based health outcomes reimbursement schemes for medical technology. METHODS We performed a review of performance-based health outcomes reimbursement schemes over the past 10 years (7/98-010/09) using publicly available databases, web and grey literature searches, and input from healthcare reimbursement experts. We developed a taxonomy of scheme types by inductively organizing the schemes identified according to the timing, execution, and health outcomes measured in the schemes. RESULTS Our search yielded 34 coverage with evidence development schemes, 10 conditional treatment continuation schemes, and 14 performance-linked reimbursement schemes. The majority of schemes are in Europe and Australia, with an increasing number in Canada and the U.S. CONCLUSION These schemes have the potential to alter the reimbursement and pricing landscape for medical technology, but significant challenges, including high transaction costs and insufficient information systems, may limit their long-term impact. Future studies regarding experiences and outcomes of implemented schemes are necessary.

Cost Effectiveness of Pharmacogenomics

The use of pharmacogenetic testing in clinical practice is limited thus far. A potential barrier to the widespread implementation of pharmacogenetic testing is the lack of evidence on whether testing provides good value for money. The objective of this review was to provide a systematic and critical review of economic evaluations of pharmacogenetic testing. A literature search using publically available databases was performed for articles published up to October 2009. To be included, studies had to meet the definition of being a pharmacogenomic study (defined as use of information on human genetic variation to target drug therapy) and an economic evaluation (defined as an evaluation of both costs and clinical outcomes). Articles that met these criteria were subsequently reviewed and graded using the Quality of Health Economic Studies (QHES) instrument. Lastly, the evidence for biomarker validity and utility were qualitatively assessed using expert opinion.A total of 34 articles were identified using our defined criteria. The most common disease category was thromboembolic-related diseases (26%), while the most common biomarkers were thiopurine methyltransferase and cytochrome P450 2C9 (18% each). Almost all studies were published after 2004 (91%). Two types of studies were identified: cost-effectiveness studies and cost-utility studies, with roughly half of the overall studies being cost-utility studies (53%) and a majority of these published within the last 3 years. The average quality score was 77 (range 29–99). Of the biomarkers reviewed, it was estimated that most had demonstrated clinical validity, but only two had demonstrated clinical utility.Despite a recent increase in the number of economic evaluations of pharmacogenetic applications, further studies examining the clinical validity and utility of these biomarkers are needed to support cost-effectiveness assessments.

Prognostic Role of ERCC1 in Advanced Non–Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

UNLABELLED Small observational studies have demonstrated an association between high ERCC1 expression level and poor prognosis in advanced NSCLC treated with platinum-based chemotherapy. This meta-analysis presents pooled estimates of association from 11 studies. High ERCC1 patients had lower response rates and higher risk of death relative to low ERCC1 patients. These results support the prognostic significance of ERCC1 expression level in advanced NSCLC. BACKGROUND Observational studies have demonstrated an association between excision repair cross-complementation group 1 (ERCC1) expression level and health outcomes in patients with advanced non-small-cell lung cancer (NSCLC) treated with platinum-based regimens. This analysis presents pooled estimates of association from these studies to better elucidate the prognostic role of ERCC1 in advanced NSCLC. METHODS A systematic literature search was conducted using the MEDLINE, EMBASE, and American Society of Clinical Oncology (ASCO) annual meeting databases from June 1995 to December 2010. Included studies were evaluated for clinical, methodological, and statistical heterogeneity. Pooled analyses were conducted using fixed and random effects models. RESULTS In high ERCC1 expression versus low ERCC1 expression patients, pooled analysis results demonstrated a significantly lower response (risk ratio [RR], 0.80, 0.66-0.98) and significantly higher risk of death (hazard ratio [HR], 2.04, (1.48-2.80)), respectively. Subgroup analyses demonstrated significant heterogeneity in outcomes by ERCC1 measurement method (I(2): 90.7%, P = 0.001) and patient population ethnicity (I(2): 66%, P = 0.003). CONCLUSION This studys findings support the hypothesis that ERCC1 expression is associated with response rate and overall survival (OS) in patients with advanced NSCLC treated with platinum-based chemotherapy. Heterogeneity in subgroup analyses demonstrates the need for standardized methods to classify ERCC1 expression level, studies evaluating the association between ERCC1 expression and OS in non-Asian populations, and studies evaluating interaction between ERCC1 and other known prognostic factors in advanced NSCLC.

Multigene assays and molecular markers in breast cancer: systematic review of health economic analyses

Breast cancer is the most common female cancer and is associated with a significant clinical and economic burden. Multigene assays and molecular markers represent an opportunity to direct chemotherapy only to patients likely to have significant benefit. This systematic review examines published health economic analyses to assess the support for adjuvant therapy decision making. Literature searches of PubMed, the Cochrane Library, and congress databases were carried out to identify economic evaluations of multigene assays and molecular markers published between 2002 and 2012. After screening and data extraction, study quality was assessed using the Quality of Health Economic Studies instrument. The review identified 29 publications that reported evaluations of two assays: Oncotype DX® and MammaPrint. Studies of both tests provided evidence that their routine use was cost saving or cost-effective versus conventional approaches. Benefits were driven by optimal allocation of adjuvant chemotherapy and reduction in chemotherapy utilization. Findings were sensitive to variation in the frequency of chemotherapy prescription, chemotherapy costs, and patients’ risk profiles. Evidence suggests that multigene assays are likely cost saving or cost-effective relative to current approaches to adjuvant therapy. They should benefit decision making in early-stage breast cancer in a variety of settings worldwide.

Value-of-information analysis within a stakeholder-driven research prioritization process in a US setting: an application in cancer genomics.

Objective. The objective of this study was to evaluate the feasibility and outcomes of incorporating value-of-information (VOI) analysis into a stakeholder-driven research prioritization process in a US-based setting. Methods. Within a program to prioritize comparative effectiveness research areas in cancer genomics, over a period of 7 months, we developed decision-analytic models and calculated upper-bound VOI estimates for 3 previously selected genomic tests. Thirteen stakeholders representing patient advocates, payers, test developers, regulators, policy makers, and community-based oncologists ranked the tests before and after receiving VOI results. The stakeholders were surveyed about the usefulness and impact of the VOI findings. Results. The estimated upper-bound VOI ranged from

An evaluation of the potential cost-effectiveness of non-invasive testing strategies in the diagnosis of significant liver fibrosis

33 million to

Epidermal growth factor receptor genomic variation in NSCLC patients receiving tyrosine kinase inhibitor therapy: a systematic review and meta-analysis

2.8 billion for the 3 research areas. Seven stakeholders indicated the results modified their rankings, 9 stated VOI data were useful, and all indicated they would support its use in future prioritization processes. Some stakeholders indicated expected value of sampled information might be the preferred choice when evaluating specific study designs. Limitations. Our study was limited by the size and the potential for selection bias in the composition of the external stakeholder group, lack of a randomized design to assess effect of VOI data on rankings, and the use of expected value of perfect information v. expected value of sample information methods. Conclusions. Value of information analyses may have a meaningful role in research topic prioritization for comparative effectiveness research in the United States, particularly when large differences in VOI across topic areas are identified. Additional research is needed to facilitate the use of more complex value of information analyses in this setting.

Stakeholder assessment of the evidence for cancer genomic tests: insights from three case studies.

Background and Aim:  To assess the clinical and economic outcomes of non‐invasive testing strategies in the diagnosis of significant liver fibrosis (Metavir score ≥ 2) compared with liver biopsy.

Predicting Low Accrual in the National Cancer Institute's Cooperative Group Clinical Trials

Introduction The objective of this analysis was to examine the relationship between genomic variation and health outcomes in studies performed in non-small cell lung cancer (NSCLC) patients treated with single agent epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) using a systematic review with statistical pooling of data.MethodsWe performed a systematic search of the literature using the MEDLINE, BIOSIS, and EMABASE databases from July 1997 to July 2007. Eligible studies were evaluated for quality and clinical, methodological, and statistical heterogeneity. Abstracted data judged to be sufficiently homogenous were pooled using a fixed effect model. ResultsWe found a statistically significant higher probability of tumor response (according to the RECIST criteria) for patients with EGFR mutations versus wild type (5.92, 95% CI 4.91–7.13) and patients with high- versus low EGFR protein expression (2.71, 95% CI 1.72–4.29). EGFR mutation and high EGFR protein expression were associated with significantly improved survival over the wild type and low protein expression groups (0.36, 95% CI 0.29–0.46 and 0.59, 95% CI 0.44–0.81), respectively. Last, there was a significant difference in EGFR-TKI treatment effect in the high EGFR gene copy number and high EGFR protein expression groups (0.72, 95% CI 0.57–0.92 and 0.53, 95% CI 0.35–0.80).ConclusionIn conclusion, EGFR mutation and protein expression status may provide useful clinical information in terms of the likelihood of tumor response and disease prognosis. EGFR gene copy number and to a lesser extent, EGFR protein expression status, appear to be promising biomarkers for predicting a survival benefit with EGFR-TKI therapy in second line NSCLC, but further evidence is needed.

Understanding the Economic Value of Molecular Diagnostic Tests: Case Studies and Lessons Learned

Purpose:Insufficient evidence on the net benefits and harms of genomic tests in real-world settings is a translational barrier for genomic medicine. Understanding stakeholders’ assessment of the current evidence base for clinical practice and coverage decisions should be a critical step in influencing research, policy, and practice.Methods:Twenty-two stakeholders participated in a workshop exploring the evidence of genomic tests for clinical and coverage decision making. Stakeholders completed a survey prior to and during the meeting. They also discussed if they would recommend for or against current clinical use of each test.Results:At baseline, the level of confidence in the clinical validity and clinical utility of each test varied, although the group expressed greater confidence for epidermal growth factor receptor mutation and Lynch syndrome testing than for Oncotype DX. Following the discussion, survey results reflected even less confidence for Oncotype DX and epidermal growth factor receptor mutation testing, but not for Lynch syndrome testing. The majority of stakeholders would consider clinical use for all three tests, but under the conditions of additional research or a shared clinical decision–making approach.Conclusion:Stakeholder engagement in unbiased settings is necessary to understand various perspectives about evidentiary thresholds in genomic medicine. Participants recommended the use of various methods for evidence generation and synthesis.Genet Med advance online publication 5 April 2012.