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臨床医薬学生物統計学

研究室概要

生物統計学(Biostatistics)は、生物・医学領域に特化した統計学の一領域であり、統計学の応用を通して、生物・医学での様々な問題の解決をめざします。大きな不確実性を伴う人での諸現象を対象とする臨床研究はもちろん、基礎研究においても生物統計学は貢献できます。疾患を問わず、様々なタイプの医学研究に横断的に関与でき、その多くで本質的な貢献ができる可能性を秘めていることが生物統計学の大きな魅力です。
本研究室では生物統計学的手法に関する研究を行っていますが、医学研究での共同研究も多く行っています。生物統計学の方法論の研究とその実践は車の両輪のようなものです。生物統計の実践から生物統計の新しい方法論の研究が生まれ、その成果からより高度な生物統計の実践が生まれます。本研究室ではこのサイクルを回していくことをめざしています。

研究プロジェクト

1. 個別化医療の開発のための統計的方法論の開発とその実践
 個別化医療開発のプロセスを、1)治療効果予測マーカーを含めた診断法の開発、2)診断法の評価(分析的・臨床的妥当性の評価)、3)診断法に基づく治療法の有効性・安全性の検証、4)医療現場での臨床有用性の評価と治療の意思決定ツールの開発の4つのフェーズに分け、臨床研究のデザインとデータ解析に関する統計的方法・ツールの開発を進めている。各種がん、関節リウマチ(自己免疫疾患)、糖尿病などの様々な疾患領域における事例研究も重点的に行うことで、個別化医療開発の現場に役立つ方法論の構築とその実践に関する総合的研究を行う。

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A)               B)


図1.1. 多発性骨髄腫のランダム化臨床試験における予後関連遺伝子と治療効果予測因子の同時検出.治療前の形質細胞の遺伝子発現マイクロアレーデータ(約5万のプローブセット)に対してサリドマイド治療追加群と非追加群での死亡リスク(対数ハザード比)を推定。5万プローブセットでの対数ハザード比のプロット(パネルA)とセミパラメトリック階層混合モデルによりノイズ成分(ノイズ遺伝子、サンプリング誤差)を取り除いた効果サイズ分布(シグナル成分)(パネルB)[1].

biostatistics02.jpg

A)              B)


図1.2. 効果予測マーカーとサリドマイドの効果(コントロール群に対する対数ハザード比)の関係(パネルA)。効果予測マーカーと予後マーカーを同時に用いた個体レベルでの生存曲線予測(パネルB)[13]。

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図1.3. 骨髄異形成症候群における遺伝子発現量に基づく疾患異質性の検出(混合モデルに基づくネスト型二方向クラスタリング)

2. 空間疫学における統計手法の開発とその実践:

保健医療分野において、疾病発生の空間的な格差・変動を明らかにするためには、それらのリスク要因の空間変動も考慮に入れた分析を行うことが必要である。特に健康リスクの兆候を早期に検出するためのいくつかのモニタリングシステムには、疾病集積性検出の解析が組み込まれている。疾病集積性の検定の代表的な方法としては、空間スキャン統計量に基づく検定法が提案され、時間、空間、時空間データなど様々なデータを対象とした集積性の検出に適用されている。これら疾病の空間情報を解析するための新たな統計的方法の開発とともに、ソフトウェアの開発、ならびに難病をはじめとする実際の疾病の地域特性の調査研究,疾病に関連した遺伝子の検出,脳画像解析,医薬品による副作用自発報告に基づくシグナル検出への適用など,幅広い分野への応用研究も進めている。

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図 2.1. 疾病集積性検定のために開発されたソフトウェア, FleXScan

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図 2.2. 心肺機能停止傷病者救急搬送件数、2005/1/1~2011/3/10までの日単位,男性・非心原性(黒実線)と期待件数(オレンジ線)、ならびに検出された有意な集積期間。 [6]

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図2.3. 精神科病院入院患者の受療移動分析マップ。各二次医療圏内における入院患者の(i) 二次医療圏内居住者割合、(ii)県内居住者割合(それぞれベイズ推定値) [2]

教員

構成員名役職所属
松井 茂之 教授 生物統計学
髙橋 邦彦 准教授 生物統計学
大谷 隆浩 特任助教 生物統計学

研究実績

  • 2019年
    1. Matsui S, Igeta M, Toyoizumi K. Biomarker-based phase II and III clinical trials in oncology. In Textbook of Clinical Trials in Oncology. (eds. S. Halabi and S. Michiels), CRC Press. 2019. (in press).
    2. Takahashi K, Takahashi H, Nakaya T, Yasumura S, Ohira T, Ohto H, Ohtsuru A, Midorikawa S, Suzuki S, Shimura H, Yamashita S, Tanigawa K, Kamiya K. Factors influencing the proportion of non-examinees in the Fukushima Health Management Survey for childhood and adolescent thyroid cancer: Results from the baseline survey. Journal of Epidemiology, 2019. (in press)
    3. Otani T, Noma H, Sugasawa S, Kuchiba A, Goto A, Yamaji T, Kochi Y, Iwasaki M, Matsui S, Tsunoda T. Exploring predictive biomarkers from clinical genome-wide association studies via multidimensional hierarchical mixture models. European Journal of Human Genetics, 2019; 27: 140-149.
    4. Kawabata T, Emoto R, Nishino J, Takahashi K, Matsui S. Two-stage analysis for selecting fixed numbers of features in omics association studies. Statistics in Medicine, 2019; 38(16): 2956-2971.
    5. Emura T, Matsui S, Rondeau V. Survival Analysis with Correlated Endpoints: Joint Frailty-Copula Models, Springer, 2019. (In press).
    6. Nonaka T, Igeta, M, Matsui S. Statistical testing strategies for assessing treatment efficacy and marker accuracy in phase III trials. Pharmaceutical Statistics, 2019. (In press)
    7. Sakai Y, Honda M, Matsui S, Komori O, Murayama T, Fujiwara T, Mizuno M, Imai Y, Yoshimura K, Nasti A, Wada T, Iida N, Kitahara M, Horii R, Tamai T, Nishikawa M, Okafuji H, Mizukoshi E, Yamashita T, Yamashita T, Arai K, Kitamura K, Kawaguchi K, Takatori H, Shimakami T, Terashima T, Hayashi T, Nio K, Kaneko S; Hokuriku Liver Study Group. Development of novel diagnostic system for pancreas cancer including early stages measuring mRNA of whole blood cells. Cancer Science, 2019. (in press)
    8. Nishikimi M, Ogura T, Nishida K, Takahashi K, Nakamura M, Matsui S, Matsuda N, Iwami T. External validation of a risk classification at the emergency department of post-cardiac arrest syndrome patients undergoing targeted temperature management. Resuscitation, 2019. (in press)
    9. Okada E, Takahashi K, Nakamura K, Ukawa S, Takabayashi S, Nakamura M, Sasaki S, Tamakoshi A, Takimoto H. Dietary patterns and impaired abnormal glucose tolerance among Japanese: findings from the National Health and Nutrition Survey, 2012. Public Health Nutrition, 2019. (in press)
    10. Liu K, Ogura T, Takahashi K, Nakamura M, Ohtake H, Fujiduka K, Abe E, Oosaki H, Miyazaki D, Suzuki H, Nishikimi M, Lefor AK, Mato T. A progressive early mobilization program is significantly associated with clinical and economic improvement: A single-center quality comparison study. Critical Care Medicine, 2019. (in press)
    11. Kasugai D, Hirakawa A, Ozaki M, Nishida K, Ikeda T, Takahashi K, Matsui S, Uenishi N. Maximum norepinephrine dosage within 24 hours as an indicator of refractory septic shock: a retrospective study. Journal of Intensive Care Medicine 2019. (in press)
    12. Komori S, Ueno S, Ito Y, Sayo A, Meinert M, Kominami T, Inooka D, Kitagawa M, Nishida K, Takahashi K, Matsui S, Terasaki H. Steeper macular curvature in eyes with non-highly myopic retinitis pigmentosa. Investigative Ophthalmology & Visual Science 2019. (in press)
    13. Emura T, Matsui S, Chen HY. compound.Cox: univariate feature selection and compound covariate for predicting survival. Computer Methods and Programs in Biomedicine, 2019, 168: 21-37.
    14. Anzai T, Takahashi K, Watanabe M. Adverse reaction reports of neuroleptic malignant syndrome induced by atypical antipsychotic agents in the Japanese Adverse Drug Event Report (JADER) database. Psychiatry and Clinical Neurosciences, 2019; 73: 27-33.
    15. Nomura K, Hiyama TY, Sakuta H, Matsuda T, Lin CH, Kobayashi K, Kobayahi K, Kuwaki T, Takahashi K, Matsui S, Noda M. Na+ increases in body fluids sensed by central Na_x induce sympathetically mediated blood pressure elevations via H+-dependent activation of ASIC1a. Neuron, 2019; 101, 60-75.
    16. Kasugai D, Nishikimi M, Nishida K, Higashi M, Yamamoto T, Numaguchi A, Takahashi K, Matsui S, Matsuda N. Timing of administration of epinephrine predicts the responsiveness to epinephrine in norepinephrine-refractory septic shock: a retrospective study. Journal of Intensive Care, 2019; 7: 20.
    17. Yamauchi T, Sasaki T, Takahashi K, Umezaki S, Takahashi M, Yoshikawa T, Suka M, Yanagisawa H. Long working hours, sleep-related problems, and near-misses/injuries in industrial settings using a nationally representative sample of workers in Japan. PLoS ONE 2019; 14(7): e0219657.
  • 2018年
    1. Matsui S, Crowley J. Biomarker-stratified phase III clinical trials: enhancement with a subgroup-focused sequential design. Clinical Cancer Research, 2018; 24: 994-1001.
    2. Matsui S, Noma H, Qu P, Yoshio Sakai, Matsui K, Heuck C, Crowley J. Multi-subgroup gene screening using semi-parametric hierarchical mixture models and the optimal discovery procedure: application to a randomized clinical trial in multiple myeloma. Biometrics, 2018; 74: 313-320.
    3. Takahashi K, Shimadzu H. Multiple-cluster detection test for purely temporal disease clustering: Integration of scan statistics and generalized linear models. PLoS ONE, 2018; 13: e0207821.
    4. Otani T, Noma H, Nishino J, Matsui S. Re-assessment of multiple testing strategies for more efficient genome-wide association studies. European Journal of Human Genetics, 2018; 26: 1038-1048.
    5. Nishino J, Ochi H, Kochi Y, Tsunoda T, Matsui S. Sample size for successful genome-wide association study of major depressive disorder. Frontiers in Genetics 2018; 9: 227.
    6. Nishino J, Kochi Y, Shigemizu D, Kato M, Ikari K, Ochi H, Noma H, Matsui K, Morizono T, Boroevich K, Tsunoda T, Matsui S. Empirical Bayes estimation of semi-parametric hierarchical mixture models for unbiased characterization of polygenic disease architectures. Frontiers in Genetics, 2018; 9: 115.
    7. Igeta M, Takahashi K, Matsui S. Power and sample size calculation incorporating misspecifications of the variance function in comparative clinical trials with over-dispersed count data. Biometrics, 2018; 74: 1459-1467.
    8. Horisaki K, Takahashi K, Ito H, Matsui S. A dose-response meta-analysis of coffee consumption and colorectal cancer risk in the Japanese population: application of a cubic-spline model. 2018; Journal of Epidemiology,28: 503-509.
    9. Hirakawa A, Sato H, Daimon T, Matsui S. Modern Dose-Finding Designs for Cancer Phase I Trials: Drug Combination and Molecularly Targeted Agents. Springer, 2018.
    10. Kuriki S, Takahashi K, Hara H. Multiplicity adjustment for temporal and spatial scan statistics using Markov property. Japanese Journal of Statistics and Data Science, 2018; 1: 191-213.
    11. Nakaya T, Takahashi K, Takahashi H, Yasumura S, Ohira T, Ohto H, Ohtsuru A, Midorikawa S, Suzuki S, Shimura H, Yamashita S, Tanigawa K, Kamiya K. Spatial analysis of the geographical distribution of thyroid cancer cases from the first-round thyroid ultrasound examination in Fukushima Prefecture. Scientific Reports, 2018; 8: 17661.
    12. Liu K, Ogura T, Takahashi K, Nakamura M, Ohtake H, Fujiduka K, Abe E, Oosaki H, Miyazaki D, Suzuki H, Nishikimi M, Kawarai-Kefor A, Mato T. The safety of a novel early mobilization protocol conducted by ICU physicians: a prospective observational study. Journal of Intensive Care, 2018; 6: 10.
    13. Nishikimi M, Ogura T, Matsui K, Takahashi K, Fukaya K, Liu K, Morita H, Nakamura M, Matsui S, Matsuda N. Accuracy of the first interpretation of early brain CT images for predicting the prognosis of post-cardiac arrest syndrome patients at the emergency department. Journal of Intensive Care, 2018; 6: 26.
    14. Okumura J, Shindo Y, Takahashi K, Sano M, Sugino Y, Yagi T, Taniguchi H, Saka H, Matsui S, Hasegawa Y. Mortality in patients with community-onset pneumonia at low risk of drug-resistant pathogens: Impact of β-lactam plus macrolide combination therapy. Respirology, 2018; 23: 526-534.
    15. Nishikimi M, Ogura T, Nishida K, Takahashi K, Fukaya K, Liu K, Nakamura M, Matsui S, Matsuda N. Differential effect of mild therapeutic hypothermia depending on the findings of hypoxic encephalopathy on early CT images in patients with post-cardiac arrest syndrome. Resuscitation, 2018; 128: 11-15.
    16. Nishikimi M, Numaguchi A, Takahashi K, Miyagawa Y, Matsui K, Higashi M, Makishi G, Matsui S, Matsuda N. Effect of administration of Ramelteon, a melatonin receptor agonist, on the duration of stay in the ICU: a single center randomized placebo-controlled trial. Critical Care Medicine, 2018; 46: 1099-1105.
    17. Fukamachi S, Hashiguchi M, Takahashi K, Mochizuki M. Exploratory evaluation of a commercially available Japanese medical record database as an external control for comparative clinical trials in new drug development: Amyotrophic lateral sclerosis. Neurology and Clinical Neuroscience, 2018; 6: 94-99.
    18. Tominaga Y, Aomori T, Hayakawa T, Kijima N, Morisky DE, Takahashi K, Mochizuki M. Possible associations of personality traits representing harm avoidance and self-directedness with medication adherence in Japanese patients with type 2 diabetes. Journal of Pharmaceutical Health Care and Sciences, 2018; 4: 16.
    19. Matsuhisa T, Takahashi N, Aomatsu M, Takahashi K, Nishino J, Ban N, Mercer SW. How many patients are required to provide a high level of reliability in the Japanese version of the CARE Measure? A secondary analysis. BMC Family Practice, 2018; 19: 138.
    20. Ogura T, Nakamura Y, Takahashi K, Nishida K, Kobashi D, Matsui S. Treatment of patients with sepsis in a closed Intensive Care Unit is associated with improved survival: A nationwide observational study in Japan. Journal of Intensive Care, 2018; 6: 57.
    21. Tominaga Y, Aomori T, Hayakawa T, Morisky DE, Takahashi K, Mochizuki M. Relationship between medication adherence and glycemic control in Japanese patients with type 2 diabetes. Pharmazie, 2018; 73: 609-612.
    22. Okada E, Takahashi K, Takimoto H, Takabayashi S, Kishi T, Kobayashi T, Nakamura K, Ukawa S, Nakamura M, Sasaki S, Tamakoshi A. Dietary patterns among Japanese adults: findings from the National Health and Nutrition Survey, 2012. Asia Pacific Journal of Clinical Nutrition, 2018; 27: 1120-1130.
    23. Shimamura F, Hamada C, Matsui S, Hirakawa A. Two-stage approach based on zone and dose findings for two-agent combination phase I/II trials. Journal of Biopharmaceutical Statistics, 2018; 8: 1-13.
    24. Emura T, Nakatochi M, Matsui S, Michimae H, Rondeau V. Personalized dynamic prediction of death according to tumour progression and high-dimensional genetic factors: Meta-analysis with a joint model. Statistical Methods in Medical Research, 2018; 27: 2842-2858.
    25. Funahashi S, Okazaki Y, Nishiyama T, Ohyoshi H, Yasui H, Nishida K, Matsui S, Toyokuni S. Global overexpression of divalent metal transporter 1 delays crocidolite-induced mesothelial carcinogenesis in male mice. Free Radical Research, 2018; 52: 1030-1039.
    26. Komura T, Yano M, Miyake A, Takabatake H, Miyazawa M, Ogawa N, Seki A, Honda M, Wada T, Matsui S, Kaneko S, Sakai Y. Immune condition of colorectal cancer patients featured by serum chemokines and gene expressions of CD4+ cells in blood. Canadian Journal of Gastroenterology and Hepatology, 2018; 7436205.
    27. Hayashi K, Oshima H, Shimizu M, Kobayashi K, Matsui S, Nishida Y, Usui A. Preoperative six-minute walk distance is associated with postoperative cognitive dysfunction. Annals of Thoracic Surgery, 2018; 106: 505-512.
    28. Kawai A, Goto T, Shibata T, Tani K, Mizutani S, Nishikawa A, Shibata T, Matsumoto S, Nagata K, Narukawa M, Matsui S, Ando M, Toguchida J, Monden M, Heike T, Kimura S, Ueda R. The current state of therapeutic development for rare cancers in Japan, and proposals for improvement. Cancer Science, 2018; 109: 1731-1737.
    29. 松井茂之. オミクス研究における検証的解析と探索的解析:多重検定とP値を中心に.計量生物学, 2018; 38, 127-139.
    30. 大谷隆浩, 菅澤翔之助, 野間久史. 希少な遺伝的変異を対象とする集約型関連解析. 計算機統計学, 2018; 31: 17-33.
    31. 山内貴史, 梅崎重夫, 平岡伸隆, 高橋邦彦, 須賀万智, 柳澤裕之. 過重労働・過労と業務上の事故. 産業医学ジャーナル, 2018; 41, 24-127.
    32. 丹後俊郎,松井茂之(編).新版医学統計学ハンドブック.朝倉書店, 2018.
    33. 高橋邦彦(翻訳,編集委員). 生物統計学, 他. 日本統計学会(翻訳)統計科学百科事典. 丸善出版, 2018.
  • 2017年
    1. Matsui S, Crowley J (editors). Frontiers of Biostatistical Methods and Applications in Clinical Oncology, Springer, 2017.
    2. Matsui S, Phase III clinical trial designs incorporating predictive biomarkers: an overview. In Frontiers of Biostatistical Methods and Applications in Clinical Oncology. (eds. S. Matsui, J. Crowley), Springer, 2017.
    3. Takahashi K, Tachimori H, Kan C, Nishi D, Okumura Y, Kato N, Takeshima T. Spatial analysis for regional behavior of patients with mental disorders in Japan. Psychiatry and Clinical Neurosciences, 2017; 71; 254-261.
    4. Toyoizumi K, Matsui S. Correcting estimation bias in randomized clinical trials with a test of treatment-by-biomarker interaction. Statistics in Biopharmaceutical Research, 2017; 9: 172-179.
    5. Noma H, Tanaka S, Matsui S, Cipriani A, Furukawa TA. Quantifying indirect evidence in network meta-analysis. Statistics in Medicine, 2017; 36: 917-927.
    6. Sugasawa S, Noma H, Otani T, Nishino J, Matsui S. An efficient and flexible test for rare variant effects. European Journal of Human Genetics, 2017; 25: 752-757.
    7. Nishikimi M, Matsuda N, Matsui K, Takahashi K, Ejima T, Liu K, Ogura T, Higashi M, Umino H, Makishi G, Numaguchi A, Matsushima S, Tokuyama H, Nakamura M, Matsui S. A novel scoreing system for predicting the neurological prognosis prior to the initiation of induced hypothermia in cases of post-cardiac arrest syndrome: the CAST score. Journal of Trauma, Resuscitation and Emergency Medicine, 2017; 25: 49.
    8. Takagishi M, Sawada M, Ohata S, Asai N, Enomoto A, Takahashi K, Weng L, Ushida K, Ara H, Matsui S, Kaibuchi K, Sawamoto K, Takahashi M. Daple coordinates 1 planar polarized microtubule dynamics in ependymal cells and contributes to hydrocephalus. Cell Reports, 2017; 20: 960-972.
    9. Sayo A, Ueno S, Kominami T, Nishida K, Inooka D, Nakanishi A, Yasuda S, Okado S, Takahashi K, Matsui S, Terasaki H. Longitudinal study of visual field changes determined by Humphrey Field Analyzer 10-2 in patients with Retinitis Pigmentosa. Scientific Reports, 2017; 7: 16383.
    10. Takahashi H, Takahashi K, Shimura H, Yasumura S, Suzuki S, Ohtsuru A, Midorikawa S, Ohira T, Ohto H, Yamashita S, Kamiya K. Simulation of expected childhood and adolescent thyroid cancer cases in Japan using a cancer-progression model based on the National Cancer Registry: application to the first-round thyroid examination of the Fukushima Health Management Survey. Medicine, 2017; 96: e8631.
    11. Okumura Y, Sakata N, Takahashi K, Nishi D, Tachimori H. Epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge in Japan: an exploratory descriptive study using a nationwide claims database. Journal of Epidemiology, 2017; 27: 373-380.
  • 2016年
    1. Nishikimi M, Matsuda N, Matsui K, Takahashi K, Ejima T, Liu K, Ogura T, Higashi M, Umino H, Makishi G, Numaguchi A, Matsushima S, Tokuyama H, Nakamura M, Matsui S. CAST: a new score for early prediction of neurological outcomes after cardiac arrest before therapeutic hypothermia with high accuracy. Intensive Care Medicine, 2016; 42: 2106-2107.
    2. Sadashima E, Hattori S, Takahashi K. Meta-analysis of prognostic studies for a biomarker with a study-specific cut-off value. Research Synthesis Methods, 2017; 7: 402-419.
    3. Ishikawa T, Uetake H, Murotani K, Kobunai T, Ishiguro M, Matsui S, Sugihara K. Genome-wide DNA copy-number analysis in ACTS-CC trial of adjuvant chemotherapy for stage III colonic cancer. Anticancer Research, 2016; 36: 853-860.
    4. Kobayashi M, Iwase T, Yamamoto K, Ra E, Murotani K, Matsui S, Terasaki H. Association between photoreceptor regeneration and visual acuity following surgery for rhegmatogenous retinal detachment. Investigative Ophthalmology & Visual Science, 2016; 57: 889-898.
    5. 竹島正, 立森久照, 高橋邦彦. 認知症施策とこれからの精神保健医療福祉のあり方. 連載:わが国の認知症施策の未来6. 老年精神医学雑誌, 2016; 27, 777-782.
    6. 竹島正, 立森久照, 高橋邦彦, 山之内芳雄. 精神保健医療福祉の改革ビジョンの成果と今後の課題. 公衆衛生, 2016; 80, 790-796.
    7. 高橋邦彦. 空間疫学への誘い-難病の地図から何が見えるか. 岩波データサイエンス刊行委員会(編). 岩波データサイエンス Vol.4. 岩波書店, 2016.
    8. 加藤直広, 立森久照, 高橋邦彦. 地図の上で階層ベイズモデリング. 岩波データサイエンス刊行委員会(編). 岩波データサイエンス Vol.4. 岩波書店, 2016
  • 2015年
    1. Matsui S, Buyse M, Simon R. (editors). Design and Analysis of Clinical Trials for Predictive Medicine. CRC Press, 2015.
    2. Matsui S, Choai Y, Nonaka T. Phase III all-comers clinical trials with a predictive biomarker. In Design and Analysis of Clinical Trials for Predictive Medicine. (eds. S. Matsui, M. Buyse, R. Simon), CRC Press, 2015.
    3. Matsui S. Statistical issues in clinical development and validation of genomic signatures. In Design and Analysis of Clinical Trials for Predictive Medicine. (eds. S. Matsui, M. Buyse, R. Simon), CRC Press, 2015.
    4. Matsui S. Development and validation of continuous genomic signatures in randomized clinical trials. In Design and Analysis of Clinical Trials for Predictive Medicine. (eds. S. Matsui, M. Buyse, R. Simon), CRC Press, 2015.
    5. Simon R, Matsui S, Buyse M. Clinical trials for predictive medicine: new paradigms and challenges. In Design and Analysis of Clinical Trials for Predictive Medicine. (eds. S. Matsui, M. Buyse, R. Simon), CRC Press, 2015.
    6. Daimon T, Hirakawa A, Matsui S. Phase I dose-finding designs and their applicability to targeted therapies. In Design and Analysis of Clinical Trials for Predictive Medicine. (eds. S. Matsui, M. Buyse, R. Simon), CRC Press, 2015.
    7. Noma H, Matsui S. Univariate analysis for gene screening: beyond the multiple testing. In Design and Analysis of Clinical Trials for Predictive Medicine. (eds. S. Matsui, M. Buyse, R. Simon), CRC Press, 2015.
    8. Takahashi K, Shimadzu H. The daily incidence of out-of-hospital cardiac arrest unexpectedly increases around New Yesar’s Day in Japan. Resuscitation, 2015; 96: 156-162.
    9. Choai Y, Matsui S. Estimation of treatment effects in all-comers randomized clinical trials with a predictive marker. Biometrics, 2015; 71: 25-32.
    10. Nomura K, Takahashi K, Hinomura Y, Kawaguchi G, Matsushita Y, Marui H, Anzai T, Hashiguchi M, Mochizuki M. Effect of database profile variation on drug safety assessment: an analysis of spontaneous adverse event reports of Japanese cases. Drug Design, Development and Therapy, 2015; 9: 3031-3041.
    11. Hirakawa A, Wages NA, Sato H, Matsui S. A comparative study of adaptive dose-finding designs for phase I oncology trials of combination therapies. Statistics in Medicine, 2015; 34: 3194-3213.
    12. Hirakawa A, Matsui S. Operating characteristics of restrictions on skipping dose level for adaptive dose-finding method in two-agent phase I trials. Japanese Journal of Biometrics, 2015; 36: 1-12.
    13. Yanagida K, Iwase T, Yamamoto K, Ra E, Kaneko H, Murotani K, Matsui S, Terasaki H. Sex-related differences in ocular blood flow of healthy subjects using laser speckle flowgraphy. Investigative Ophthalmology & Visual Science, 2015; 56: 4880-4890.
    14. Sugimoto T, Matsumoto T, Hosoi T, Miki T, Gorai I, Yoshikawa H, Tanaka Y, Tanaka S, Fukunaga M, Sone T, Nakano T, Ito M, Matsui S, Yoneda T, Takami H, Watanabe K, Osakabe T, Okubo N, Shiraki M, Nakamura T. Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT). Osteoporosis International, 2015; 26: 765-774.
    15. Takanari K, Araki Y, Okamoto S, Sato H, Yagi S, Toriyama K, Yokotyama K, Murotani K, Matsui S, Wakabayashi T, Kamei Y. Operative wound related complications after cranial revascularization surgeries. Journal of Neurosurgery, 2015; 123: 1145-1150.
    16. Iwase T, Yamamoto K, Ra E, Murotani K, Matsui S, Terasaki H. Diurnal variations in blood flow at optic nerve head and choroid in healthy eyes: diurnal variations in blood flow. Medicine, 2015; 94: e519.
  • 2014年
    1. Matsui S, Choai Y, Nonaka T. Comparison of statistical analysis plans in randomize-all phase III trials with a predictive biomarker. Clinical Cancer Research, 2014; 20: 2820-2830.
    2. Nakashima T, Sato H, Gyo K, Hato N, Yoshida T, Shimono M, Teranishi M, Sone M, Fukunaga Y, Kobashi G, Takahashi K, Matsui S, Ogawa K. Idiopathic sudden sensorineural hearing loss in Japan. Acta Oto-Laryngologica, 2014; 134: 1158--1163.
    3. Kubokawa T, Hasukawa M, Takahashi K. On measuring uncertainty of benchmarked predictors with application to disease risk estimate. Scandinavian Journal of Statistics, 2014; 41: 394-413.
    4. Ogino D, Takahashi K, Sato H. Characteristics of clinical trial websites: information distribution between ClinicalTrials.gov and 13 primary registries in the WHO registry network. Trials, 2014; 15: 428.
  • 2013年
    1. Matsui S. Genomic biomarkers for personalized medicine: development and validation in clinical studies. Computational and Mathematical Methods in Medicine, 2013; Article ID: 865980.
    2. Takahashi K, Nakao H, Hattori S. Cubic spline regression of J-shaped dose-response curves with likelihood-based assignments of grouped exposure levels. Journal of Biometrics & Biostatistics, 2013; 4: 181.
    3. Yokomichi H, Yokoyama T, Takahashi K, Yoshiike N, Yamagata Z, Tango T. An improved statistical method to estimate usual intake distribution of nutrients by age group. Journal of Nutrition & Food Sciences, 2013; 3: 196.
  • 2012年
    1. Matsui S, Simon R, Qu P, Shaughnessy J, Barlogie B, Crowley J. Developing and validating continuous genomic signatures in randomized clinical trials for predictive medicine. Clinical Cancer Research, 2012; 18: 6065-6073.
    2. Tango T, Takahashi K. A flexible spatial scan statistic with a restricted likelihood ratio for detecting disease clusters. Statistics in Medicine, 2012; 31: 4207-4218.
  • 2011年
    1. Matsui S, Noma H. Estimation and selection in high-dimensional genomic studies for developing molecular diagnostics. Biostatistics, 2011; 12: 223-233.
    2. Matsui S, Noma H. Estimating effect sizes of differentially expressed genes for power and sample size assessments in microarray experiments. Biometrics, 2011; 67: 1225-1235.
    3. Nishiyama T, Takahashi K, Tango T, Pinto D, Scherer SW, Takami S, Kishino H. A scan statistic to extract causal gene clusters from case-control genome-wide rare CNV data. BMC Bioinformatics, 2011; 12: 205.
    4. Tango T, Takahashi K, Kohriyama K. A space-time scan statistic for detecting emerging outbreaks. Biometrics, 2011; 67: 106-115.

研究キーワード

医学研究のデザインとデータ解析、バイオマーカー・診断法の開発、ゲノムデータ解析、 個別化医療、空間疫学、メタアナリシス

その他

名大生物統計学に興味のある方は教室HPをご覧ください。
大学院入学を希望される方へ:出身分野は問いませんが、統計学・数学についての一定の知識が前提となります(目安として統計検定二級)。