Alternative methods of evaluating treatment effect in case of correlated competing risks in clinical trials

• Project/Area Number: 16K12400
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Statistical science
• Research Institution: Niigata University
• Principal Investigator: Akazawa Kohei 新潟大学, 医歯学総合病院, 教授 (10175771)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 生存時間解析 / 競合リスク / 無再発期間 / ログランク検定 / 比例ハザードモデル / 治療効果判定 / モンテカルロシミュレーション / 多変量回帰モデル / 無再発時間 / 複合エンドポイント / ハザードモデル / 医療統計学 / 臨床試験 / 治療効果

Outline of Final Research Achievements

The results of this study is following: (1) We estimated the frequencies of cause of death (cancer-related death, progressive failure of physical condition, other causes of death), and investigated a relationship between progression-free survival and overall survival; (2) The properties of logrank test such as size of test and power were evaluated by statistical simulation, in case of the presence of competing risks in cause-specific survival analysis; (3) We found out the statistical problems on applying logrank test and Cox proportional hazards model for multiple endpoints.

Academic Significance and Societal Importance of the Research Achievements

第Ⅱ相、第Ⅲ相臨床試験を計画する際に、評価尺度の選定はその試験デザインをほぼ決定する。代理評価尺度を主要評価尺度として採用する場合に、真の評価尺度との関連の度合いを定量的に把握できれば、不必要な代理評価尺度を選定せずに済み、臨床試験の質を向上させる可能性がある。逆に、代理評価尺度が真の評価尺度と強い関連を持つのであれば、副次評価尺度として生存期間の長期追跡調査は不要となり、臨床試験期間の短縮、試験費用の軽減、新薬の早期の承認につながる。

Research Products

• [Journal Article] Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial (2018)
  • Author(s): Kudo M、Ueshima K、Yokosuka O、Ogasawara S、Obi S、Izumi N、Aikata H、Nagano H、Hatano E、Sasaki Y、Hino K、Kumada T、Yamamoto K、Imai Y、Iwadou S、Ogawa C、Okusaka T、Kanai F、Akazawa K、Yoshimura K、Johnson P、Arai Y
  • Journal Title: The Lancet Gastroenterology & Hepatology Volume: 3 Issue: 6 Pages: 424-432
  • DOI: 10.1016/s2468-1253(18)30078-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001-2007) (2017)
  • Author(s): Katai H, Ishikawa T, Akazawa K, Isobe Y, Miyashiro I, Oda I, Tsujitani S, Ono H, Tanabe S, Fukagawa T, Nunobe S, Kakeji Y, Nashimoto A; Registration Committee of the Japanese Gastric Cancer Association
  • Journal Title: Gastric Cancer Volume: 17 Issue: 1 Pages: 144-154
  • DOI: 10.1007/s10120-017-0716-7
  • NAID: 40021436651
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study (2017)
  • Author(s): Azumi M, Suda T, Terai S, Akazawa K.
  • Journal Title: Internal Medicine Volume: 56 Issue: 9 Pages: 1001-1007
  • DOI: 10.2169/internalmedicine.56.7278
  • NAID: 130005632054
  • ISSN: 0918-2918, 1349-7235
  • Open Access
• [Journal Article] Optimal treatment strategy for acute cholecystitis based on predictive factors: Japan-Taiwan multicenter cohort study (2017)
  • Author(s): Endo Itaru、Takada Tadahiro、Hwang Tsann-Long、Akazawa Kohei、Mori Rintaro、Miura Fumihiko、Yokoe Masamichi、Itoi Takao、Gomi Harumi、Chen Miin-Fu、Jan Yi-Yin、Ker Chen-Guo、Wang Hsiu-Po、Kiriyama Seiki、Wada Keita、Yamaue Hiroki、Miyazaki Masaru、Yamamoto Masakazu
  • Journal Title: Journal of Hepato-Biliary-Pancreatic Sciences Volume: 24 Issue: 6 Pages: 346-361
  • DOI: 10.1002/jhbp.456
  • Open Access
• [Journal Article] Percutaneous and endoscopic gallbladder drainage for the acute cholecystitis: International multicenter comparative study by a propensity score-matched analysis. (2017)
  • Author(s): Itoi T, Takada T, Hwang TL, Endo I, Akazawa K, Miura F, Chen MF, Jan YY, Ker CG, Wang HP, Gomi H, Yokoe M, Kiriyama S, Yamaue H, Miyazaki M, Yamamoto M.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: in press Issue: 6 Pages: 362-368
  • DOI: 10.1002/jhbp.454
  • Peer Reviewed / Open Access
• [Journal Article] Survival outcomes of neoadjuvant chemotherapy with zoledronic acid for HER2-negative breast cancer (2017)
  • Author(s): Ishikawa Takashi、Akazawa Kouhei、Hasegawa Yoshie、Tanino Hirokazu、Horiguchi Jun、Miura Daishu、Hayashi Mitsuhiro、Kohno Norio
  • Journal Title: Journal of Surgical Research Volume: 220 Pages: 46-51
  • DOI: 10.1016/j.jss.2017.05.066
  • Open Access
• [Journal Article] Re-evaluating Cut-off Points for the Expansion of Deceased Donor Criteria for Kidney Transplantation in Japan. (2017)
  • Author(s): Nakagawa.Y, Ikeda.M, Ando.T, Tasaki.M, Saito.K,Takahashi.K, Aikawa.A, Kikuchi.M, Akazawa.K, Tomita.Y.
  • Journal Title: Transplantation Proceedings Volume: 49(1) Pages: 10-15
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Comparison of Number Versus Ratio of Positive Lymph Nodes in the Assessment of Lymph Node Status in Extrahepatic Cholangiocarcinoma. (2016)
  • Author(s): Sakata J, Wakai T, Matsuda Y, Ohashi T, Hirose Y, Ichikawa H, Kobayashi T, Minagawa M, Kosugi S, Koyama Y, Akazawa K, Ajioka Y.
  • Journal Title: Ann Surg Oncol. Volume: 23(1) Pages: 225-234
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Nomogram for 5-year relapse-free survival of a patient with advanced gastric cancer after surgery. (2016)
  • Author(s): Muneoka Y, Akazawa K, Ishikawa T, Ichikawa H, Nashimoto A, Yabusaki H, Tanaka N, Kosugi SI, Wakai T.
  • Journal Title: Int J Surg. Volume: 35 Pages: 153-159
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Body mass index and menopausal disorders during menopause affect vasomotor symptoms of postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes. (2016)
  • Author(s): Tane K, Egawa C, Takao S, Yamagami K, Miyashita M, Baba M, Ichii S, Konishi M, Kikawa Y, Minohata J, Okuno T, Miyauchi K, Wakita K, Suwa H, Hashimoto T, Nishino M, Matsumoto T, Hidaka T, Konishi Y, Sakoda Y, Miya A, Kishimoto M, Nishikawa H, Kono S, Kokufu I, Sakita I, Kitatsuji K, Oh K, Akazawa K, Miyoshi Y.
  • Journal Title: Breast Cancer. Volume: -
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials. (2016)
  • Author(s): Kroep JR, Charehbili A, Coleman RE, Aft RL, Hasegawa Y, Winter MC, Weilbaecher K, Akazawa K, Hinsley S, Putter H, Liefers GJ, Nortier JW, Kohno N.
  • Journal Title: Eur J Cancer Volume: 54 Pages: 57-63
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Utility of comprehensive genomic sequencing for detecting HER2-positive colorectal cancer (2016)
  • Author(s): Shimada Y, Yagi R , Kameyama H , Nagahashi M, Ichikawa H, Tajima Y , Okamura T , Nakano M, Nakano M, Sato Y , Matsuzawa T , Sakata J, Kobayashi T, Nogami H, Maruyama S, Takii Y , Kawasaki T , Homma K, Izutsu H, Kodama K, Jennifer E. Ring, Alexei Protopopov , Stephen Lyle, Okuda S, Akazawa K, Wakai T
  • Journal Title: Human PATHOLOGY Volume: -
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Lobectomy and limited resection in small-sized peripheral nonsmall cell lung cancer (2016)
  • Author(s): Koike T , Koike T, Sato S , Hashimoto T , Aoki T , Yoshiya K , Yamato Y , Watanabe T , Akazawa K , Toyabe S , Tsuchida M ; for the Niigata Chest Surgery Research Group
  • Journal Title: Journal of Thoracic Disease. Volume: 8(11) Pages: 3265-3274
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant