Oncology Market Research Provides a Feasible Index for Standardization of Colorectal Cancer Chemotherapy

Transcription

1 Jpn J Clin Oncol 2011;41(10) doi: /jjco/hyr123 Oncology Market Research Provides a Feasible Index for Standardization of Colorectal Cancer Chemotherapy Yasuhiro Inoue, Yuji Toiyama, Koji Tanaka, Keiichi Uchida, Yasuhiko Mohri and Masato Kusunoki * Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie , Japan *For reprints and all correspondence: Masato Kusunoki, Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Edobashi, Tsu, Mie , Japan. kusunoki@clin.medic.mie-u.ac.jp Received January 19, 2011; accepted August 1, 2011 Objective: Measures to evaluate standardization of cancer therapy after the major revision of guidelines for treatment of cancer are not well established. Our objective was to evaluate the usefulness of oncology market research for measuring the effect of the guidelines on standardization of colorectal cancer chemotherapy. Methods: The source of data for this analysis was the Oncology Analyzer TM, which provides insight into oncology markets worldwide. We compared colorectal cancer chemotherapy before (July 2008 June 2009) and after the major revision (July 2009 June 2010) of the Japanese guideline in 2009 to determine the effect of the new guidelines on clinical practice. A total of 1425 patients were enrolled. Results: We confirmed that guideline revision had an effect on drug treatment. Regimens used were in agreement with the recommendations of the new guidelines, except that some characteristics depended on hospital specialization. A time-course study in 1 year also showed evident change in the use of colorectal cancer chemotherapy by the third quarter after the revision. Conclusions: Oncology market research is a useful tool for evaluating standardization of colorectal cancer chemotherapy. Furthermore, we expect that this method will contribute to the development of more effective cancer therapies. Key words: colorectal cancer chemotherapy oncology market standardization INTRODUCTION Worldwide, more than 1 million individuals develop colorectal cancer (CRC) every year (1). CRC is a major health problem in the Western world and the second most common cause of cancer mortality (2). To improve outcomes, the role of chemotherapy for CRC has expanded considerably during the past decade. Although surgery remains the mainstay of treatment, the vast majority of patients with CRC now receive chemotherapy with multiple agents that are presently approved for treatment in the relevant setting. However, it is a complex process to select the optimal chemotherapy for each patient and the evidence practice gap is still a problem. We used the IMS Health Oncology Analyzer TM to carry out a comprehensive comparative study on the characteristics of CRC chemotherapy around the world. The Analyzer provides insight into the oncology market of seven countries: the USA, five nations of the European Union (EU) and Japan (3). We found large differences in regimens by institution, region and country. The results suggest that the evidence practice gap for CRC chemotherapy still exists around the world. Recently, standardization of cancer treatment, including chemotherapy, has become of particular importance for the quality of cancer therapy and has been promoted by the # The Author (2011). Published by Oxford University Press. All rights reserved.

2 1204 Market research and guidelines for cancer therapy Japanese Cancer Control Act in In 2009, the Japanese guidelines for the treatment of CRC were further revised to promote the standardization of CRC treatment. It is important to know whether the major revision achieved standardization of CRC chemotherapy. Measures and indicators of its quality are needed and several studies on quality indicators of cancer care have been reported (4,5). However, measures to evaluate standardization of cancer therapy are not well established. In this study, we evaluated the usefulness of oncology market research to assess the evidence practice gap in CRC chemotherapy. We also discuss the role of the method for measuring the effect of standardization of CRC chemotherapy. PATIENTS AND METHODS DATA SOURCES The data source for this analysis was the Oncology Analyzer TM (IMS Health Oncology, Fairfield, CT, USA), which provides insight into the worldwide oncology market. It is an easy-to-use market research tool that has been designed to monitor various cancer treatments. It segments patients by indication, stage and line of therapy to provide an understanding of patient pathways, prescribers, products, prescribing initiation and treatment practice patterns. The Oncology Analyzer TM tracks the use of chemotherapy, hormonal therapy, radiotherapy, surgery and supportive therapies. Patient data are recorded and collected using paper diary studies. These provide a full treatment history, from diagnosis to the present day and include surgery, radiotherapy, chemotherapy, hormonal therapy and supportive care reports. SAMPLING Data for Japan are collected via a survey methodology in which physicians complete data collection forms for a number of patients per quarter. Based on their workload, physicians are asked to provide case histories for the last 5 25 patients they have seen and are requested not to provide the same patient s details twice in any 12-month period. Data collection covers all aspects of the patient s chemotherapy treatment, from diagnosis, assignment of therapy, date of therapy and details of the therapy administered to full demographics, which include disease stage at diagnosis and at relapse. Regular reporting by a panel of physicians ensures that the data are up-to-date. Participating physicians are recruited from key hospitals and oncology centers. They have different levels of experience, ranging from registrar to consultant. These lead to a variety of attitudes and approaches to treatment and prescribing. In Japan, the panel consists of over 1300 physicians; the average is 200 per country. The target coverage is 70% of major cancer centers. The criterion to become a panel physician was experience in CRC chemotherapy for six patients or more per week, and physicians practiced in both general (49%) and specialized (51%) hospitals. To ensure the accuracy of the market survey, regular reporting per quarter by panel physicians was limited to six patients each and the accuracy of all reports was also checked by staff with an exclusive contract using an interview conducted by visits, telephone or . TREATMENT GUIDELINES FOR CRC IN JAPAN The Japanese Society for Cancer of the Colon and Rectum (JSCR) guidelines for the treatment of CRC were first published in June 2005 to promote the standardization of CRC treatment (6). The JSCR guidelines, published in June 2009, were revised based on the latest evidence (7). Table 1 shows the differences in the regimens adopted after the first and second publications (6,7). Almost all disadvantages associated with drug approval in Japan were resolved in this major revision. Only two drugs, panitumumab and first-line cetuximab were still the cause for contention. They were approved, however, later in Bevacizumab or capecitabine combined with oxaliplatin is used for treatment of advanced and recurrent CRC, while the FOLFOX regimen is used for patients with a high risk of recurrence in adjuvant chemotherapy. In this major revision, current controversies are addressed as clinical questions with several references. Table 1. Differences in the regimens adopted after revision of the Japanese guidelines for colorectal cancer treatment in 2009 JSCR guidelines, 2005 (5) JSCR guidelines, 2009 (6) Adjuvant chemotherapy 5-FU/LV 5-FU/LV, UFT/LV UFT (UFT/LV, capecitabine) a Capecitabine Oxaliplatin based (FLOX, FOLFOX, etc.) b Therapeutic chemotherapy First line First line 5-FU/LV, UFT/LV, S-1 5-FU/LV + bevacizumab IFL, FOLFIRI FOLFOX + bevacizumab FOLFOX FOLFIRI + bevacizumab UFT/LV Second line Second line FOLFIRI, FOLFOX, IFL FOLFOX + bevacizumab UFT/LV, S-1, 5 0 DFUR, etc. FOLFIRI + bevacizumab FOLFIRI + cetuximab CPT-11 JSCR, Japanese Society for Cancer of the Colon and Rectum; FU, fluorouracil; LV, leucovorin; UFT, tegafur uracil. a Introduced as foreign evidence. b Irinotecan-based chemotherapy should not be used.

3 Jpn J Clin Oncol 2011;41(10) 1205 It seems likely that many physicians in Japan, including those who cooperated in the market research, used the JSCR guidelines as a reference in selecting CRC therapy, since the JSCR guidelines have large circulation sales in Japan, with copies before the major revision in 2009 and copies for the year following the major revision. STANDARDIZATION OF CRC CHEMOTHERAPY AFTER MAJOR REVISION OF JAPANESE GUIDELINES IN 2009 Several anticancer drugs, including molecular-targeted drugs, were disapproved for use in the 2009 revision. We compared CRC chemotherapy before (July 2008 June 2009) and after the major revision (July 2009 June 2010) to evaluate the effect of the new guidelines on standardization of CRC chemotherapy in Japan. RESULTS A total of 1425 patients with CRC were enrolled in our study from July 2008 to June Of these participants, 880 with Stage IV CRC received therapeutic chemotherapy. The other 545 patients with Stage III CRC received adjuvant chemotherapy. FIRST-LINE CHEMOTHERAPY FOR STAGE IV CRC Figure 1 shows the use of first-line chemotherapy for Stage IV CRC. Among the 880 patients, 477 underwent therapeutic chemotherapy before the revision of the JSCR guidelines and 403 patients underwent therapeutic chemotherapy after the revision. We confirmed large differences in regimens after its publication. Regimens with bevacizumab- or capecitabine-related regimens, such as capecitabine plus oxaliplatin with or without bevacizumab regimens, were frequently administered after the revision of the guidelines. In contrast, irinotecan-based regimens, especially FOLFIRI alone, were infrequently used as a first-line chemotherapy. Standardization of CRC chemotherapy was independent of hospital specialization. The chemotherapy regimens among cancer centers, university hospitals and general hospitals resembled each other, but there were large differences among these institutions before the revision of the guidelines (Fig. 2a c). General hospitals still favored the use of oral fluoropyrimidines, such as UFT/LV (tegafur uracil/ leucovorin) and S-1 compared with the other institutions. ADJUVANT CHEMOTHERAPY FOR STAGE III CRC Figure 3 shows the use of adjuvant chemotherapy for Stage III CRC. Among the 545 patients, 261 underwent adjuvant chemotherapy before the revision of the JSCR guidelines and 284 underwent adjuvant chemotherapy after. Regimens used were in agreement with the recommendations of the new guidelines. Approval for a new regimen of oxaliplatinbased chemotherapy was granted and the use of S-1 had decreased because of a lack of evidence. We also investigated whether adjuvant chemotherapy regimens differed between specialized and non-specialized hospitals (Fig. 4a c). Data showed that the use of chemotherapy in cancer centers and general hospitals was similar, but university hospitals had different approaches. They used oral drugs, such as doxifluridine and polysaccharide-k, despite a lack of evidence related to their adjuvant use. GROWTH IN GUIDELINE APPLICATION Data revealed the change over time in standardization of CRC chemotherapy. The collected data of prescriptions were analyzed quarterly to evaluate the time-course expansion of the new guideline s effects. In both therapeutic and adjuvant chemotherapy, the expansion of the new guideline s effects on actual treatments were time dependent (Fig. 5a andb). The characteristic change in the use of CRC chemotherapy was evident by the third quarter after the revision. Figure 1. Comparison of first-line chemotherapy for Stage IV colorectal cancer (CRC) before and after the major revision of the JSCR guidelines for the treatment of CRC. LV, leucovorin; BEVA, bevacizumab; CAPEC, capecitabine, OXAL, oxaliplatin, IRN, irinotecan. DISCUSSION This study assessed the usefulness of oncology market research to evaluate the standardization of CRC chemotherapy. The methodology enabled the understanding of regimens used for CRC chemotherapy worldwide. Findings showed large differences in regimens between countries, regions and institutions (3). Reasons for the evidence practice gap include historical characteristics that favor the use of 5-FU/LV infusion in the EU, molecular-targeting agents in the USA and oral fluoropyrimidines in Japan. Oral

4 1206 Market research and guidelines for cancer therapy Figure 2. Comparison of the actual use of regimens for Stage IV CRC among (a) cancer centers (b), university hospitals and (c) and general hospitals. Figure 3. Comparison of adjuvant chemotherapy for Stage III CRC before and after major revision of the JSCR guidelines for the treatment of CRC. fluoropyrimidines, such as UFT, 5 0 DFUR and S-1 are used in Japan despite a lack of evidence related to their use in CRC treatment. This might be because most patients are treated by surgeons, because of a shortage of oncologists in Japan. Furthermore, the actual use of CRC chemotherapy can depend on the healthcare policies of the respective governments. Approval of several anticancer agents in Japan, for example, had been lagging behind those that in the USA and the EU until the revision in The present study compared the actual uses of CRC chemotherapy before and after the major revision of the Japanese guidelines in This was after almost all disadvantages associated with drug approval in Japan had been resolved. Consequently, we confirmed that the guideline revision had an effect on drug treatment in Japan. Regimens used were in line with the recommendations of the new guidelines, except some characteristics depended on hospital specialization. In first-line chemotherapy for Stage IV CRC, general hospitals still favored the use of oral fluoropyrimidines, such as UFT/LV and S-1. Nonetheless, differences among general hospitals, cancer centers and university hospitals decreased after the guideline revision. In adjuvant chemotherapy for Stage III CRC, cancer centers and general hospitals used similar regimens, but those used in university hospitals

5 Jpn J Clin Oncol 2011;41(10) 1207 Figure 4. Comparison of chemotherapy for Stage III CRC among (a) cancer centers, (b) university hospitals and (c) general hospitals. Figure 5. The time-course expansion of the new guideline s effects on therapeutic chemotherapy for (a) Stage IV CRC and (b) adjuvant chemotherapy for Stage III CRC. differed. This might be due to the large number of independent studies conducted in university hospitals in Japan. Measures and indicators are greatly needed to evaluate and improve the quality of cancer treatment. In 1999, the National Cancer Policy Board called attention to the quality of cancer care in the USA, and recommended establishing a quality monitoring system with the capability to regularly report on the quality of care for patients

6 1208 Market research and guidelines for cancer therapy with cancer (8). The National Initiative on Cancer Care Quality was one of the most comprehensive studies to look at the quality of cancer care in the USA (9). It is expected that information from measuring the standardization of cancer therapy could be used to improve the quality of cancer therapy. However, reliable measures to evaluate standardization of cancer therapy are still not established. Using market research to establish indicators for the standardization of cancer care is a new methodology. Data not only showed the evidence practice gap, but also the growth of standardization of CRC chemotherapy as affected by treatment guidelines. The methodology indicates a lack of standardization in CRC care. Oncology market research also has the potential for cost-effective analyses, as the sales data for each agent can be evaluated using the oncology-analyzing system. In conclusion, oncology market research is a useful tool for measuring the standardization of cancer therapy. Furthermore, we expect that this method will contribute to the advent of more effective therapy from both oncological and economic viewpoints. Acknowledgements We thank Tsutomu Miyazawa, Tamayo Hirouchi, Yoshifumi Kondo and Takashi Mori for analyzing the data. Funding This work was supported by the IMS Japan Corporation. Conflict of interest statement None declared. References 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, CA Cancer J Clin 2005;55: Ries LA, Wingo PA, Miller DS, Howe HL, Weir HK, Rosenberg HM, et al. The annual report to the nation on the status of cancer, , with a special section on colorectal cancer. Cancer 2000;88: Inoue Y, Toiyama Y, Tanaka K, Miki C, Kusunoki M. A comprehensive comparative study on the characteristics of colorectal cancer chemotherapy. Jpn J Clin Oncol 2009;39: McGory ML, Shekelle PG, Ko CY. Development of quality indicators for patients undergoing colorectal cancer surgery. JNatlCancerInst 2006;98: Leonardi MJ, McGory ML, Ko CY. Quality of care issues in colorectal cancer. Clin Cancer Res 2007;13:6897s 902s. 6. Japanese Society for Cancer of the Colon and Rectum. Japanese Society for Cancer of the Colon and Rectum. JSCCR Guidelines 2005 for the Treatment of Colorectal Cancer. Tokyo: Kanehara Co Japanese Society for Cancer of the Colon and Rectum. Japanese Society for Cancer of the Colon and Rectum. JSCCR Guidelines 2009 for the Treatment of Colorectal Cancer. Tokyo: Kanehara Co Hewitt M, Simone J. National Cancer Policy Board, Institute of Medicine: Ensuring Quality Cancer Care. Washington, DC: National Academy Press Bailes JS. ASCO s groundbreaking study on cancer care quality: NICCQ. J Oncol Pract 2006;2:48.