Annual Report 2018

Division of Biostatistical Research

Taro Shibata, Aya Kuchiba

Introduction

 Biostatisticians at the NCC have two key roles. The first is to contribute to providing best evidence as scientists through planning and implementing statistical designs and methods, and providing statistical considerations in every stage of a subject-matter research project. The second is to developing novel statistical and mathematical methods, motivated by methodological issues that arise in various scientific disciplines. While the Biostatistics Division at the Center for Research Administration and Support makes comprehensive efforts to work on both roles, the Division of Biostatistical Research at the Center for Public Health Sciences particularly focuses on the second role and responsibility.

Research activities

 Investigators in the Division of Biostatistical Research are actively working on identifying and solving statistical problems, and developing novel methodology in various research areas.

1. Epidemiology and Prevention Research Area

 We are involved in the study for evaluating the association of serum biomarkers with cancer risk using case-cohort study design. We also review the methods for causal mediation analysis with a potential outcome framework to get deeper insights into the mechanism of cancer development. In addition, we are working on developing prediction models for major cancer in Japanese people.

2. Survivorship Research Area

 We are involved in projects on breast cancer survivors: the questionnaire survey on physical activity and the development of exercise programs. We have worked on the study protocols and the study design papers.

3. Clinical Research Area

▹ Development and utilization of clinical trial database
We are regularly updating information on ongoing clinical trials by establishing collaborative relationships with other sources of providing cancer information and the project teams of cancer research.

▹ Support system for endoscopic diagnosis with artificial intelligence
We are developing the study protocols for evaluating the diagnostic performance of support systems for endoscopic diagnosis with artificial intelligence. We have also worked on research papers for diagnostic performance evaluation using exiting image data.

▹ Reliability of real world data (RWD) and patient registry/study design and statistical methods for utilizing RWD
In the projects supported by AMED, we provide perspectives on the requirement for reliability of RWD and patient registry data for pharmaceutical approval. We also review the study designs and statistical methods for utilizing RWD.

4. Methodological Research

▹ Prediction performance for multi-category
We are working on developing methods to assess prediction performance for outcomes with more than two categories (e.g., breast cancer with ER+, breast cancer with ER-, no cancer). The preliminary results of examining characteristics of the proposed index have been submitted for presentation at the international statistical conference (3rd Pacific Rim Cancer Biostatistics Conference 2019). We are working on finalizing the research paper.

▹ Latent subgroup
We have launched the project on the statistical method to detect latent subgroups for treatment response.

Future prospects

 Biostatistics has a close connection with real applications. Working on both methodological projects and real applications is important for future developments of biostatistical research. In 2018, we started to study the new area of dissemination and implementation (D&I) research, in addition to the above. We are reviewing the study design and statistical methodology.

 We endeavor to establish a powerful collaborative relationship with researchers throughout the NCC and to identify critical issues that the NCC needs to tackle.

List of papers published in 2018

Journal

 1. Nozaki M, Kagami Y, Shibata T, Nakamura K, Ito Y, Nishimura Y, Kawaguchi Y, Saito Y, Nagata Y, Matsumoto Y, Akimoto T, Hiraoka M. A primary analysis of a multicenter, prospective, single-arm, confirmatory trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906. Jpn J Clin Oncol, 49:57-62, 2019

 2. 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. Eur J Hum Genet, 27:140-149, 2019

 3. Hidaka A, Budhathoki S, Yamaji T, Sawada N, Tanaka-Mizuno S, Kuchiba A, Charvat H, Goto A, Shimazu T, Inoue M, Noda M, Tsugane S, Iwasaki M. Plasma C-peptide and glycated albumin and subsequent risk of cancer: From a large prospective case-cohort study in Japan. Int J Cancer, 144:718-729, 2019

 4. Ishikawa M, Nakamura K, Shibata T, Tanaka K, Kitagawa R, Kobayashi H, Yaegashi N. A randomized phase II/III trial of conventional paclitaxel and carboplatin with or without bevacizumab vs dose-dense paclitaxel and carboplatin with or without bevacizumab, in stage IVB, recurrent or persistent cervical carcinoma: Japan Clinical Oncology Group Study (JCOG1311). Jpn J Clin Oncol, 48:1096-1100, 2018

 5. Kodaira T, Kagami Y, Shibata T, Shikama N, Nishimura Y, Ishikura S, Nakamura K, Saito Y, Matsumoto Y, Teshima T, Ito Y, Akimoto T, Nakata K, Toshiyasu T, Nakagawa K, Nagata Y, Nishimura T, Uno T, Kataoka M, Yorozu A, Hiraoka M. Results of a multi-institutional, randomized, non-inferiority, phase III trial of accelerated fractionation versus standard fractionation in radiation therapy for T1-2N0M0 glottic cancer: Japan Clinical Oncology Group Study (JCOG0701). Ann Oncol, 29:992-997, 2018

 6. Hishida T, Saji H, Watanabe SI, Asamura H, Aokage K, Mizutani T, Wakabayashi M, Shibata T, Okada M. A randomized Phase III trial of lobe-specific vs systematic nodal dissection for clinical Stage I-II non-small cell lung cancer (JCOG1413). Jpn J Clin Oncol, 48:190-194, 2018

 7. Miyamoto K, Fukuhara N, Maruyama D, Shibata T, Nakamura K, Ishizawa K, Tsukasaki K, Nagai H. Phase III study of watchful waiting vs rituximab as first-line treatment in advanced stage follicular lymphoma with low tumour burden (JCOG1411, FLORA study). Jpn J Clin Oncol, 48:777-780, 2018

 8. Hirakawa A, Nishikawa T, Yonemori K, Shibata T, Nakamura K, Ando M, Ueda T, Ozaki T, Tamura K, Kawai A, Fujiwara Y. Utility of Bayesian Single-Arm Design in New Drug Application for Rare Cancers in Japan: A Case Study of Phase 2 Trial for Sarcoma. Ther Innov Regul Sci, 52:334-338, 2018

 9. Kimbara S, Fujiwara Y, Iwama S, Ohashi K, Kuchiba A, Arima H, Yamazaki N, Kitano S, Yamamoto N, Ohe Y. Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab. Cancer Sci, 109:3583-3590, 2018

 10. 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. Current state of therapeutic development for rare cancers in Japan, and proposals for improvement. Cancer Sci, 109:1731-1737, 2018