Blood Forum Value of innovation in hematologic malignancies: a systematic review of published cost-effectiveness analyses Cayla J. Saret, 1 Aaron N. Winn, 2 Gunjan Shah, 3 Susan K. Parsons, 3 Pei-Jung Lin, 1 Joshua T. Cohen, 1 and Peter J. Neumann 1 1 Center for the Evaluation of Value and Risk in Health, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA; 2 Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC; and 3 Center for Health Solutions, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA We analyzed cost-effectiveness studies related to hematologic malignancies from the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org), fo- cusing on studies of innovative therapies. Studies that met inclusion criteria were cate- gorized by 4 cancer types (chronic myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and multiple mye- loma) and 9 treatment agents (interferon-a, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide). We examined study characteristics and stratified cost-effectiveness ratios by type of cancer, treatment, funder, and year of study publication. Twenty-nine studies pub- lished in the years 1996-2012 (including 44 cost-effectiveness ratios) met inclusion cri- teria, 22 (76%) of which were industry funded. Most ratios fell below $50 000 per quality-adjusted life-years (QALY) (73%) and $100 000/QALY (86%). Industry-funded studies (n 5 22) reported a lower median ratio ($26 000/QALY) than others (n 5 7; $33 000/ QALY), although the difference was not sta- tistically significant. Published data suggest that innovative treatments for hematologic malignancies may provide reasonable value for money. (Blood. 2015;125(12):1866-1869) Introduction During the past 15 years, treatment of hematologic malignancies changed radically. In 1997, the US Food and Drug Administration approved rituximab, now widely used to treat hematologic malig- nancies, including non-Hodgkin lymphoma (NHL). Later, tyrosine kinase inhibitors (TKIs) were introduced to treat chronic myeloid leukemia (CML). TKIs exceeded survival benefit expectations 1 ; however, they also have a notably high cost. The first TKI, imatinib, was introduced in 2001 at roughly $30 000/y of treatment. Others, introduced more recently, cost roughly $100 000/y or more. 2 These prices have prompted significant outcry, with some questioning whether these medications provide good value for money. 2 The use of bortezomib (a proteasome inhibitor) and the novel anti- angiogenesis agent lenalidomide have improved multiple myeloma (MM) outcomes. These and other innovative treatments have increased patients’ life expectancy. 1,3 Cost-effectiveness analysis (CEA) is a technique to assess the ben- efit of interventions relative to their costs. Cost-utility analysis (CUA) is a type of CEA that measures health benefits in quality-adjusted life- years (QALYs). This generic measure facilitates comparison of health care interventions addressing varied conditions. CUA has been used extensively in oncology. 4 We identified innovative treatments for hematologic malignan- cies and performed a systematic review of peer-reviewed CUAs. It is important to understand the current literature regarding these treatments, which have undergone dramatic changes in cost and effectiveness. We synthesized analyses of care for hematologic malignancies; examined the number, quality, and related character- istics of analyses; and summarized cost-utility ratios by treatment and disease types. To our knowledge, this review is the first of its kind. Methods We analyzed data from the Tufts Medical Center CEA Registry (www.cearegistry. org), a database of over 9800 cost-effectiveness ratios published in the peer- reviewed medical and economic literature through 2012. The Registry’s development and inclusion criteria are described elsewhere. 5 Briefly, English- language publications identified by a MEDLINE search that contain an original cost per QALY estimate were retrieved. Two trained researchers evaluated articles for inclusion and extracted article information. Disagree- ment was resolved by consensus. Our review included studies that addressed treatment of hematologic malignancies. We excluded review, editorial, or methodologic articles; CEAs that did not measure health effects in QALYs; and non-English-language articles. We included therapeutic agents that the US Food and Drug Administration approved since 1997 and excluded hematopoietic stem cell transplant, symptom management, and supportive care. The studies were manually checked for du- plication. No duplicates were found. We collected data regarding study origin, methods, and reporting of results. For each CUA, descriptive characteristics collected included publication year, country of origin, intervention type, publication journal, funding source, and methodologic and analytic characteristics including study perspective, discount- ing of future costs and life-years, whether economic data were collected alongside a clinical trial, and type of sensitivity analysis performed (ie, univariate, multivariable, or probabilistic). Each study was assigned a subjective quality score on a Likert scale from 1 (low) to 7 (high), based on rigor of methodology, presentation, and value to decision makers. We conducted a subgroup analysis of incremental cost-effectiveness ratio (ICER) distributions that included only quality scores that were high ($5) and compared this analysis to the distribution in all studies. To facilitate comparison of standardized outcomes, non–United States cur- rencies were converted into United States dollars using the appropriate foreign exchange factor for the relevant year, and ratios were inflated to 2012 dollars using the general Consumer Price Index. Submitted July 31, 2014; accepted December 15, 2014. Prepublished online as Blood First Edition paper, February 5, 2015; DOI 10.1182/blood-2014-07- 592832. The online version of this article contains a data supplement. The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 USC section 1734. © 2015 by The American Society of Hematology 1866 BLOOD, 19 MARCH 2015 x VOLUME 125, NUMBER 12 For personal use only. on May 2, 2017. by guest www.bloodjournal.org From