Open Access Research BMJ Open: first published as 10.1136/bmjopen-2016-011322 on 6 June 2016. Downloaded from Longitudinal trends in use and costs of targeted therapies for common cancers in Taiwan: a retrospective observational study Jason C Hsu,1 Christine Y Lu2 To cite: Hsu JC, Lu CY. ABSTRACT Strengths and limitations of this study Longitudinal trends in use Objectives: Some targeted therapies have improved and costs of targeted survival and overall quality of cancer care generally, but ▪ therapies for common This is the first study to examine the national these increasingly expensive medicines have led to cancers in Taiwan: a trend in use and costs of targeted therapies for retrospective observational increases in pharmaceutical expenditure. This study treatment of cancer in Taiwan. study. BMJ Open 2016;6: examined trends in use and expenditures of ▪ We also determined which cancer types e011322. doi:10.1136/ antineoplastic agents in Taiwan, and estimated market accounted for the highest use of targeted therap- bmjopen-2016-011322 shares by prescription volume and costs of targeted ies in Taiwan, from 2009 to 2012. therapies over time. We also determined which cancer ▪ Data were retrieved from Taiwan’s National ▸ Prepublication history and types accounted for the highest use of targeted Health Insurance Research Database with nearly additional material is therapies. 99% of the Taiwanese population (around 23 available. To view please visit Design: This is a retrospective observational study million residents) enrolled and 97% of hospitals the journal (http://dx.doi.org/ focusing on the utilisation of targeted therapies for and clinics throughout the country included. 10.1136/bmjopen-2016- treatment of cancer. ▪ A time series design with Autoregressive 011322). Setting: The monthly claims data for antineoplastic Integrated Moving Average (ARIMA) models was agents were retrieved from Taiwan’s National Health used in this study, to estimate the trends in Insurance Research Database (2009–2012). market shares by prescription volume and costs Received 29 January 2016 of targeted therapies. Revised 28 April 2016 Main outcome measures: We calculated market shares by prescription volume and costs for each class ▪ Owing to the lack of patient-level data, this study Accepted 18 May 2016 http://bmjopen.bmj.com/ of antineoplastic agent by cancer type. Using a time did not investigate the use of combination treat- series design with Autoregressive Integrated Moving ments; these need to be examined in future Average (ARIMA) models, we estimated trends in use studies. and costs of targeted therapies. Results: Among all antineoplastic agents, use of targeted therapies grew from 6.24% in 2009 to this percentage is expected to increase.12In 12.29% in 2012, but their costs rose from 26.16% to Taiwan, cancer is a leading cause of mortality 41.57% in that time. Monoclonal antibodies and and the annual number of patients with protein kinase inhibitors contributed the most cancer has been growing.3 In 2011, ∼92 682 on October 6, 2021 by guest. Protected copyright. (respectively, 23.84% and 16.12% of costs for individuals were diagnosed with cancer – antineoplastic agents in 2012). During 2009 2012, (male: 56%, female: 44%). Most common lung (44.64% of use; 28.26% of costs), female breast cancers in Taiwan were female breast cancer, (16.49% of use; 27.18% of costs) and colorectal (12.11% of use; 13.16% of costs) cancers accounted colorectal cancer, liver cancer, lung cancer 1 for the highest use of targeted therapies. and prostate cancer. In the same year, School of Pharmacy and ∼ Institute of Clinical Pharmacy Conclusions: In Taiwan, targeted therapies are 42 559 patients died of cancer (male: 64%, and Pharmaceutical Sciences, increasingly used for different cancers, representing a female: 36%), accounting for 28% of all College of Medicine, National substantial economic burden. It is important to deaths. Major cancers causing mortality were Cheng Kung University, establish mechanisms to monitor their use and lung cancer, liver cancer, colorectal cancer, Tainan City, Taiwan 2 outcomes. female breast cancer and oral/pharyngeal Department of Population 3 Medicine, Harvard Medical cancer. School and Harvard Pilgrim Cancer care has improved substantially and Health Care Institute, Boston, INTRODUCTION the average life expectancy has increased in Massachusetts, USA Cancer is a major public health issue glo- the past two decades, due to preventative 4 5 Correspondence to bally. Approximately 7.4 million people die strategies, early diagnosis, advances in Dr Jason C Hsu; of cancer each year worldwide, which medical technologies (including surgery and 6 [email protected] accounts for 13% of all-cause mortality, and medications) and clinical management. Hsu JC, Lu CY. BMJ Open 2016;6:e011322. doi:10.1136/bmjopen-2016-011322 1 Open Access Traditionally, chemotherapies are the main medicines for increasingly adopting patient access schemes (also BMJ Open: first published as 10.1136/bmjopen-2016-011322 on 6 June 2016. Downloaded from cancer. But these drugs are not specific to the target, and known as managed entry agreements or risk-sharing therefore often cause serious adverse effects including arrangements) to enable patient access to needed medi- neutropaenia, anaemia and thrombocytopaenia.7 In the cines, while ensuring that financing systems are sustain- last decade, however, many new anticancer drugs, so able.35 36 The performance of managed entry called targeted therapies,8 have become available. These agreements, however, is largely unknown because most drugs differ from standard chemotherapy in that they have not been evaluated.33 Major challenges at present target specific vulnerable nodes in molecular pathways;910 for many health systems include determining what pro- thus, they are generally less toxic than traditional che- portion of the healthcare budget should be allocated for motherapies.11 For some cancers, targeted therapies are treatment of cancer, including budget for targeted ther- becoming the main treatments, for example, trastuzumab apies, and designing and implementing new models for for early-stage and human epidermal growth factor recep- pricing, reimbursement, funding and utilisation deci- tor 2 (HER2) positive metastatic breast cancer.12 13 sions for cancer medicines.37 Dozens of targeted therapies have become available in In Taiwan, economic evaluation has, since 2007, been recent years and many are in the drug development pipe- part of the health technology assessment to evaluate line.14 While some have demonstrated improvements in new drugs, to determine decisions for coverage by the progression-free survival, other agents have provided National Health Insurance (NHI).38 39 In addition, prior minimal or no gains in overall survival; for instance, sora- authorisation is required for many cancer medicines, fenib, sunitinib, temsirolimus, everolimus, bevacizumab, especially for targeted therapies with high reimburse- pazopanib and axitinib for renal cell cancer.15 ment prices. An application for prior authorisation can Changes in the cancer treatment paradigm are accom- be made to the NHI system, and the drug will be reim- panied by significant economic consequences. Targeted bursed if authorisation is given.40 For instance, accord- therapies are expensive, typically costing from US$4500 ing to ‘Directions of Drug Restricted Benefit for to >US$10 000 per treatment month, even if they dem- National Health Insurance’, two targeted therapies, gefi- onstrate only improvements in progression-free survival tinib and erlotinib, for treatment of lung cancer, have – without marked gains in overall survival.15 20 The been reimbursed since 2004 and 2007, respectively. In increasing costs of new targeted cancer therapies the beginning, both were restricted to be used as third- have risen 10 times during the last decade.21 Given the line treatment, that is, patients must first have been number of new cancer medicines in development and treated with platinum and docetaxel or paclitaxel likely continual increases in drug prices, pricing of new chemotherapy, and must have had locally advanced or anticancer drugs is a real concern for accessibility and metastatic adenocarcinoma of the lung.41 affordability across all countries.15 22 23 Some have sug- Little is known about the utilisation and economic gested that a minimum of improvement in median sur- impacts of targeted cancer therapies in Taiwan. The aim http://bmjopen.bmj.com/ vival of at least 3–6 months by new cancer medicines of our longitudinal analyses was to address this gap by compared with current standards is required for the new examining the recent trend in utilisation and expendi- agent to be considered as advanced and funded at tures of cancer treatments, including targeted therapies, higher prices.24 Furthermore, because of the much higher in Taiwan. We also identified which types of cancer costs of targeted therapies compared with conventional accounted for the highest use of targeted therapies. chemotherapy—while the number of eligible patients (due to molecular subtyping) for individual agents is generally small—in aggregate, costs of targeted therapies as a group METHODS on October 6, 2021 by guest. Protected copyright. is an important contributor to growing expenditures for Data sources cancer treatments and an important issue of sustainability Taiwan’s National Health Insurance Research Database – for all healthcare systems.25 27 provided data for this study. The