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Development and application of statistical methods for small clinical trials

Research Project

Project/Area Number 18K11187
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 60030:Statistical science-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Gosho Masahiko  筑波大学, 医学医療系, 教授 (70701019)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords小標本バイアス / スパースデータバイアス / ロバスト分散 / データ欠測 / シグナル検出 / スパースデータ / ロジスティック回帰分析 / 既存データ / 混合効果モデル / 加速モデル / 多重代入法 / Bartlett補正 / ブートストラップ法 / 小標本問題 / 臨床試験 / データベース研究 / シミュレーション実験 / 小規模臨床試験 / 経時測定データ / ロバスト推測
Outline of Final Research Achievements

The purpose of this study is to develop and apply statistical methods to small clinical trials and databases with a small number of events, for which it is difficult to accumulate sufficient data. During the four-year study period, we proposed statistical methods to correct for bias and test size caused by small samples and rare events. We also studied on statistical analysis for detecting signals with small number of events in adverse drug report databases. We published 19 papers in peer-reviewed international journals based on our study results.

Academic Significance and Societal Importance of the Research Achievements

治療法が確立されていない希少疾患や小児分野の臨床試験では,必要十分な数の被験者の集積が極めて難しいため,試験規模は必然的に小さくなる.本研究では,データが十分に集積できない状況の中で,より正確で効率的な統計手法を開発し,実データに応用することでその実用性を確認した.本研究で挙げた成果は,データ集積が困難な臨床試験や臨床研究並びに医学系データベース研究全般に適用可能であるため,統計科学にとどまらず,医学の発展に大きく寄与するものである.

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (29 results)

All 2023 2022 2021 2020 2019 2018

All Journal Article (18 results) (of which Peer Reviewed: 18 results,  Open Access: 5 results) Presentation (11 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Bias in Odds Ratios From Logistic Regression Methods With Sparse Data Sets2023

    • Author(s)
      Gosho Masahiko、Ohigashi Tomohiro、Nagashima Kengo、Ito Yuri、Maruo Kazushi
    • Journal Title

      Journal of Epidemiology

      Volume: 33 Issue: 6 Pages: 265-275

    • DOI

      10.2188/jea.JE20210089

    • NAID

      130008091644

    • ISSN
      0917-5040, 1349-9092
    • Year and Date
      2023-06-05
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Using horseshoe prior for incorporating multiple historical control data in randomized controlled trials2022

    • Author(s)
      Ohigashi Tomohiro、Maruo Kazushi、Sozu Takashi、Gosho Masahiko
    • Journal Title

      Statistical Methods in Medical Research

      Volume: - Issue: 7 Pages: 1392-1404

    • DOI

      10.1177/09622802221090752

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Practical Review and Comparison of Modified Covariance Estimators for Linear Mixed Models in Small‐sample Longitudinal Studies with Missing Data2021

    • Author(s)
      Gosho Masahiko、Noma Hisashi、Maruo Kazushi
    • Journal Title

      International Statistical Review

      Volume: 89 Issue: 3 Pages: 550-572

    • DOI

      10.1111/insr.12447

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] bcmixed: A Package for Median Inference on Longitudinal Data with the Box?Cox Transformation2021

    • Author(s)
      Maruo Kazushi、Ishii Ryota、Yamaguchi Yusuke、Gosho Masahiko
    • Journal Title

      The R Journal

      Volume: 13 Issue: 2 Pages: 153-153

    • DOI

      10.32614/rj-2021-083

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Methods for detecting outlying regions and influence diagnosis in multi-regional clinical trials2021

    • Author(s)
      Aoki Makoto、Noma Hisashi、Gosho Masahiko
    • Journal Title

      Biostatistics & Epidemiology

      Volume: 5 Issue: 1 Pages: 30-48

    • DOI

      10.1080/24709360.2021.1921944

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Covariate Omission in Randomised Controlled Trials: A Review and Simulation Study2021

    • Author(s)
      Ishii Ryota、Maruo Kazushi、Gosho Masahiko
    • Journal Title

      International Statistical Review

      Volume: 90 Issue: 1 Pages: 100-117

    • DOI

      10.1111/insr.12468

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Statistical Inference Based on Accelerated Failure Time Models Under Model Misspecification and Small Samples2020

    • Author(s)
      Ishii Ryota、Maruo Kazushi、Noma Hisashi、Gosho Masahiko
    • Journal Title

      Statistics in Biopharmaceutical Research

      Volume: - Issue: 4 Pages: 384-394

    • DOI

      10.1080/19466315.2020.1752297

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Assessment of Hazard Ratios in Oncology Clinical Trials Terminated Early for Superiority2020

    • Author(s)
      Shimura Masashi、Nomura Shogo、Wakabayashi Masashi、Maruo Kazushi、Gosho Masahiko
    • Journal Title

      JAMA Network Open

      Volume: 3 Issue: 6 Pages: e208633-e208633

    • DOI

      10.1001/jamanetworkopen.2020.8633

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Borrowing external information to improve Bayesian confidence propagation neural network2020

    • Author(s)
      Tada Keisuke、Maruo Kazushi、Isogawa Naoki、Yamaguchi Yusuke、Gosho Masahiko
    • Journal Title

      European Journal of Clinical Pharmacology

      Volume: 76 Issue: 9 Pages: 1311-1319

    • DOI

      10.1007/s00228-020-02909-w

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Outlier detection and influence diagnostics in network meta‐analysis2020

    • Author(s)
      Noma Hisashi、Gosho Masahiko、Ishii Ryota、Oba Koji、Furukawa Toshi A.
    • Journal Title

      Research Synthesis Methods

      Volume: 11 Issue: 6 Pages: 891-902

    • DOI

      10.1002/jrsm.1455

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] An application of the mixed‐effects model and pattern mixture model to treatment groups with differential missingness suspected not‐missing‐at‐random2020

    • Author(s)
      Gosho Masahiko、Maruo Kazushi
    • Journal Title

      Pharmaceutical Statistics

      Volume: 20 Issue: 1 Pages: 93-108

    • DOI

      10.1002/pst.2058

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] A note on the bias of standard errors when orthogonality of mean and variance parameters is not satisfied in the mixed model for repeated measures analysis2020

    • Author(s)
      Maruo Kazushi、Ishii Ryota、Yamaguchi Yusuke、Doi Masaaki、Gosho Masahiko
    • Journal Title

      Statistics in Medicine

      Volume: 39 Issue: 9 Pages: 1264-1274

    • DOI

      10.1002/sim.8474

    • NAID

      120007132671

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multiple imputation for longitudinal data in the presence of heteroscedasticity between treatment groups2019

    • Author(s)
      Yamaguchi Yusuke、Ueno Mai、Maruo Kazushi、Gosho Masahiko
    • Journal Title

      Journal of Biopharmaceutical Statistics

      Volume: 30 Issue: 1 Pages: 178-196

    • DOI

      10.1080/10543406.2019.1632878

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Improved Small Sample Inference Methods for a Mixed-Effects Model for Repeated Measures Approach in Incomplete Longitudinal Data Analysis2019

    • Author(s)
      Ukyo Yoshifumi、Noma Hisashi、Maruo Kazushi、Gosho Masahiko
    • Journal Title

      Stats

      Volume: 2 Issue: 2 Pages: 174-188

    • DOI

      10.3390/stats2020013

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rhabdomyolysis risk from the use of two-drug combination of antidyslipidemic drugs with antihypertensive and antidiabetic medications: a signal detection analysis2018

    • Author(s)
      Gosho Masahiko
    • Journal Title

      Fundamental & Clinical Pharmacology

      Volume: 印刷中 Issue: 3 Pages: 339-346

    • DOI

      10.1111/fcp.12435

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] SignalDetDDI: An SAS macro for detecting adverse drug-drug interactions in spontaneous reporting systems2018

    • Author(s)
      Gosho Masahiko、Ohigashi Tomohiro、Maruo Kazushi
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 11 Pages: e0207487-e0207487

    • DOI

      10.1371/journal.pone.0207487

    • NAID

      120007133525

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Risk of Hypoglycemia After Concomitant Use of Antidiabetic, Antihypertensive, and Antihyperlipidemic Medications: A Database Study2018

    • Author(s)
      Gosho Masahiko
    • Journal Title

      The Journal of Clinical Pharmacology

      Volume: 58 Issue: 10 Pages: 1324-1331

    • DOI

      10.1002/jcph.1147

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of heteroscedasticity between treatment groups on mixed-effects models for repeated measures2018

    • Author(s)
      Gosho Masahiko、Maruo Kazushi
    • Journal Title

      Pharmaceutical Statistics

      Volume: 17 Issue: 5 Pages: 578-592

    • DOI

      10.1002/pst.1872

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 薬物相互作用評価のための類薬の情報を利用したシグナル検出法の提案2021

    • Author(s)
      多田圭佑,丸尾和司,五所正彦
    • Organizer
      2020年度日本計量生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 既存試験データを用いたhorseshoe prior に基づく二値応答の群間比較法2021

    • Author(s)
      大東智洋,丸尾和司,寒水孝司,五所正彦
    • Organizer
      2020年度日本計量生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 第1段階と第2段階の評価変数が異なるアダプティブシームレスデザインのためのmid-p値に基づく解析2021

    • Author(s)
      高橋健一,石井亮太,丸尾和司,五所正彦
    • Organizer
      2020年度日本統計関連学会連合大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 主要評価項目が2つの試験にglobal testを用いる際の試験データに基づく重みの最適化2021

    • Author(s)
      吉田哲,山口祐介,丸尾和司,五所正彦
    • Organizer
      2020年度日本統計関連学会連合大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 評価変数が2値変数の場合のアダプティブシームレスデザインに対する解析方法の提案2020

    • Author(s)
      高橋健一,石井亮太,丸尾和司,五所正彦
    • Organizer
      日本統計関連学会連合大会
    • Related Report
      2020 Research-status Report
  • [Presentation] ランダム化比較試験における非調整解析の影響2020

    • Author(s)
      石井亮太,丸尾和司,五所正彦
    • Organizer
      日本統計関連学会連合大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 医薬品副作用データ解析における外部情報を利用した薬物間相互作用の検出法2020

    • Author(s)
      多田圭佑,丸尾和司,五所正彦
    • Organizer
      日本統計関連学会連合大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 欠測データの解析のための混合効果モデル~理論,実践,課題2019

    • Author(s)
      五所正彦
    • Organizer
      2019年度統計関連学会連合大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Nonparametric approach with small-sample adjustment in accelerated failure time model2019

    • Author(s)
      Ishii, R, Maruo, K., Gosho, M.
    • Organizer
      40th Annual Conference of the International Society for Clinical Biostatistics, Leuven, Belgium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Modified Bayesian Confidence Propagation Neural Network for Signal Detection Analysis2019

    • Author(s)
      Tada, K., Maruo, K., Isogawa, N., Yanaguchi, Y., Gosho, M.
    • Organizer
      The 6th International Symposium on Biopharmaceutical Statistics
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 類薬の情報を利用した Bayesian Confidence Propagation Neural Network の改良法の提案2018

    • Author(s)
      多田圭介,丸尾和司,五十川直樹,五所正彦
    • Organizer
      日本計算機統計学会 第32回シンポジウム
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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