RESEARCH: 

Statistical Methods for Calculating Sample size in Clinical Trials with Multiple Endpoints

Use of co-primary endpoints (CPE) in clinical trials has been increasingly common as use of CPE could capture a more complete characterization of the effect of an intervention. Applications include infectious diseases, Alzheimer disease, irritable bowel syndrome, migraine, acute heart and failure, Duchenne and Becker muscular dystrophy, and diabetes mellitus. CPE means that a trial is designed to evaluate if the test intervention is superior (or noninferior) to the control on all primary endpoints. Failure to demonstrate superiority on any single endpoint implies that superiority to the control intervention cannot be concluded. In many CPE trials, the sample size is often unnecessarily large and impractical. Dr. Hamasaki has developed methodologies for the design, monitoring and analyses of clinical trials with CPE.

The determination of sample size and the evaluation of power are fundamental and critical elements in the design of a clinical trial. If a sample size is too small then important effects may not be detected, while a sample size that is too large is wasteful of resources and unethically puts more participants at risk than necessary. Recent clinical trials often include more than one endpoint as primary (multiple primary endpoints). Although they offer an attractive design feature to capture a more complete characterization of the intervention effects and provide more informative intervention comparisons, however multiple primary endpoints create new challenges in design and analysis of clinical trials, especially in sample size determination. Dr. Hamasaki and his research team have developed the methods for calculating sample sizes in clinical trials with multiple primary endpoints, when (i) all of the endpoints are continuous, (ii) all of the endpoints are binary, (iii) all of the endpoints are time-to-event, (iv) the endpoints are mixed continuous and binary, and (v) the endpoints are mixed time-to-event and binary.

1. Hamasaki T, Evans SR, Asakura K. Design, data monitoring and analysis of clinical trials with co-primary endpoints: A review. Journal of Biopharmaceutical Statistics 2018; 28:28-51. PMCID: PMC6135538
2. Sugimoto T, Hamasaki T, Evans SR, Sozu T. Sizing clinical trials when comparing bivariate time-to-event outcomes. Statistics in Medicine 2017; 36:1363-1382. PMCID: PMC5533151.
3. Hamasaki T, Sugimoto T, Evans SR, Sozu T. Sample size determination for clinical trials with co-primary outcomes. Exponential event-times. Pharmaceutical Statistics 12, 28-34, 2013. PMCID: PMC3770150.
4. Sugimoto T, Sozu T, Hamasaki T, Evans SR. A logrank test-based method for sizing clinical trials with two co-primary time-to-events endpoints. Biostatistics 2013; 14:409-421. PMCID: PMC4148615.
5. Sozu T, Sugimoto T, Hamasaki T. Sample size determination in clinical trials with multiple co-primary binary endpoints. Statistics in Medicine 2010; 29: 2169-2179. PMID: 20687162.

Statistical Methods for Monitoring Clinical Trials with Multiple Objectives

Recent clinical trials are often design to evaluate multiple objectives. Dr. Hamasaki and his research team have developed the statistical methods to monitor such clinical trials for efficacy or futility using group-sequential and adaptive methodologies. The methodologies have the potential to streamline clinical trials making them more efficient, i.e., offering potentially fewer required trial to participants, shortening the duration of clinical trials, and reducing costs. He and his reseach team have discussed serval decision-making strategies for rejecting or accepting an intersection-union or union-intersection hypothesis associated with multiple objectives in a group-sequential setting. He and his research team have evaluated the operating characteristics of the strategies in terms of the power and Type I error rate. He and his research team have also developed methods for sample size recalculation based on observed data at an interim, corresponding to each strategy.

1. Hamasaki T, Hung HMJ, Hsiao CF, Evans SR. On selecting the critical boundary functions in group-sequential trials with two time-to-event outcomes. Contemporary Clinical Trials 10.1016/j.cct.2020.106244
2. Asakura K, Evans SR, Hamasaki T. Interim monitoring for Futility in clinical trials with two co-primary endpoints using prediction. Statistics in Biopharmaceutical Research 2020; 12:164-175.

3. Sugimoto T, Hamasaki T, Evans SR, Halabi S. Group-sequential logrank methods for trial designs using bivariate non-competing event time outcomes. Lifetime Data Analysis 2020; 26:266–291.

4. Asakura K, Hamasaki T, Evans SR. Interim evaluation of efficacy or futility in group-sequential trials with multiple co-primary endpoints. Biometrical Journal 2017; 59:703–731. PMID: 27757980
5. Ochiai T, Hamasaki T, Evans SR, Asakura K, Ohno Y. Group-sequential three-arm noninferiority clinical trial designs. Journal of Biopharmaceutical Statistics 2017; 27:1-24. PMCID: PMC4990829
6. Hamasaki T, Asakura K, Evans SR, Sugimoto T, Sozu T. Group sequential strategies for clinical trials with multiple co-primary endpoints. Statistics in Biopharmaceutical Research 2015; 7:36-54. PMCID: PMC4382106
7. Asakura K, Hamasaki T, Sugimoto T, Hayashi K, Evans SR, Sozu T. Sample size determination in group-sequential clinical trials with two co-primary endpoints. Statistics in Medicine 2014; 33:2897–2913. PMCID: PMC4082481

Statistical Methods for Design and Analysis of Multi-reginal Clinical Trials

Recently, clinical trials across multiple regions of the world, so-called “multi-regional clinical trials” (MRCTs), have become a common practice in the shift to the simultaneous development of medical products on a global scale. A use of MRCT for medical product development has great benefit to the creation of solid evidence regarding the safety and efficacy of drugs, to more efficient and cost-effective development, and to a resolution of the “drug lag” or “medical device lag” with simultaneous worldwide registration. Drug or medical device lag means, for example, circumstances in which drugs or medical devices already approved in the EU, US or other regions have not yet been approved and have not been made available to patients in Japan over a long period of time. Dr. Hamasaki and his research team have discussed practical issues in the design, implementation, analysis, and interpretation of MRCTs and developed the methods for overcome the issues. Methods include those for assessing the consistency of treatment effects across regions and for calculating the sample size in MRCTs.

1. Hamasaki T, Wu YJ, Hsiao CF. Multiple endpoints in multiregional clinical trials, Chapter 17, In Simultaneous Global New Drug Development; Multi-Regional Clinical Trials after ICH E17, eds by: Gang Li et al. London, 2021, CRC Press.
2. Huang WS, Hung NH, Hamasaki T, Hsiao CF. Sample size determination for a specific region in multiregional clinical trials with multiple co-primary endpoints. PLoS ONE 2017; 12:e01804052017. PMCID: PMC5493407
3. Ando Y, Hamasaki T. Practical issues and lessons learned from multi-regional clinical trials via case examples. A Japanese perspective. Pharmaceutical Statistics 2010; 9:190-200. PMID: 20737442
4. Goto M, Hamasaki T. Practical issues and observations on the use of foreign clinical data in the drug development. Journal of Biopharmaceutical Statistics 2002; 12: 369-384. PubMed PMID: 12448578
5. Hamasaki T, Isomura T, Baba M, Goto M. Statistical approaches to detecting dose-response relationships. Drug Information Journal 2000; 34:579-590.

Other Statistical Methodologies

Dr. Hamasaki and his research team have developed several statistical methodologies including: (i) Box-Cox transformation to confined and censored nonnormal responses in regression, and (ii) partition testing in confirmatory adaptive designs with structured objectives, and (iii) Cox cure regression and related method for survival data. Also he has contributed to develop (iv) a trial design that compares strategies consistent with clinical practice, decision-rules that guides empiric and definitive therapy decisions in antibiotic trials, (v) methods for analyzing ordered time to event composite endpoints.

1. Evans SR, Follmann D, Liu Y, Holland T, Doernberg SB, Rouphael N, Hamasaki T, Jiang Y, Lok JL, Tran TTT, Harris AD, Fowler, Jr. VG, Boucher H, Kreiswirth BN, Bonomo RA, van Duin D, Paterson DL, Chambers H. Sequential Multiple Assignment Randomized Trials for COMparing Personalized Antibiotic StrategieS (SMART-COMPASS). Clinical Infectious Disease 2019; 68:1961-1967. PMID: 30351426
2. Follmann D, Fay M, Hamasaki T, Evans SR. Analysis of ordered composite endpoints. Statistics in Medicine 2020; 39:602-616.
3. Sugitani T, Hamasaki T, Hamada C. Partition testing in confirmatory adaptive designs with structured objectives. Biometrical Journal 2013; 55:341–359. PMID: 23576221.

4. Arano I, Sugimoto T, Hamasaki T, Ohno Y. Practical application of cure mixture model to long-term censored survivor data from a withdrawal clinical trial of patients with major depressive disorder. BMC Medical Research Methodology 2010; 10:33.

5. Hamasaki T, Kim SY. Box and Cox power-transformation to confined and censored nonnormal responses in regression. Computational Statistics & Data Analysis 2007; 51:3788-3799.
6. Sugimoto T, Hamasaki T. Properties of estimators for baseline hazard functions in a semiparametric cure model. Annals of the Institute of Statistical Mathematics 2006; 58:647-674.
7. Yin X, Hamasaki T, Evans SR.Sequential Multiple Assignment Randomized Trials for COMparing Personalized Antibiotic StrategieS (SMART COMPASS): Design considerations.Statistics in Biopharmaceutical Research 2020. doi.org/10.1080/19466315.2020.1822206

PUBLICATIONS: 

Statistical Methodology Research Publications (Selected Papers)

Hamasaki T, Hung HMJ, Hsiao CF, Evans SR. On selecting the critical boundary functions in group-sequential trials with two time-to-event outcomes. Contemporary Clinical Trials 2021;101:106244. Abstract

Yin X, Hamasaki T, Evans SR. Sequential Multiple Assignment Randomized Trials for COMparing Personalized Antibiotic StrategieS (SMART COMPASS): Design considerations. Statistics in Biopharmaceutical Research 2021; 13:181-191. Abstract

Follmann D, Fay MP,  Hamasaki T, Evans SR. Analysis of ordered composite endpoints. Statistics in Medicine 2020; 39:602-615. Abstract

Asakura K, Evans SR, Hamasaki T. Interim monitoring for futility in clinical trials with two co-primary endpoints using prediction. Statistics in Biopharmaceutical Research 2020; 12:164-175. Abstract

Sugimoto T, Hamasaki T, Evans SR, Halabi S. Group-sequential logrank methods for trial designs using bivariate non-competing event time outcomes. Lifetime Data Analysis 2020; 26:266–291. Abstract

Evans SR, Follmann D, Liu Y, Holland T, Doernberg SB, Rouphael N, Hamasaki T, Jiang Y, Lok J, Harris A, Fowler V, van Duin D, Patterson D, Chambers H. Sequential multiple assignment randomized trials for comparing personalized antibiotic strategies (SMART-COMPASS). Clinical Infectious Disease 2019; 68:1961-1967. Abstract

Hamasaki T, Evans SR, Asakura K. Design, data monitoring and analysis of clinical trials with co-primary endpoints: A review. Journal of Biopharmaceutical Statistics 2018; 28:28-51. Abstract

Huang WS, Hung HN, Hamasaki T, Hsiao CF. Sample size determination for a specific region in multiregional clinical trials with multiple co-primary endpoints. PLoS ONE 2017; 12:e01804052017. Abstract

Sugimoto T, Hamasaki T, Evans SR, Sozu T. Sizing clinical trials when comparing bivariate time-to-event outcomes. Statistics in Medicine 2017; 36:1363-1382. Abstract

Asakura K, Hamasaki T, Evans SR. Interim evaluation of efficacy or futility in group-sequential trials with multiple co-primary endpoints. Biometrical Journal 2017; 59:703-731. Abstract

Ochiai T, Hamasaki T, Evans SR, Asakura K, Ohno Y. Group-sequential three-arm noninferiority clinical trial designs. Journal of Biopharmaceutical Statistics 2017; 27:1-24. Abstract

Sozu T, Sugimoto T, Hamasaki T.Reducing unnecessary measurements in clinical trials with multiple primary endpoints. Journal of Biopharmaceutical Statistics 2016; 26:631-643. Abstract

Ando Y, Hamasaki T, Asakura K, Evans SR, Sugimoto T, Sozu T, Ohno, Y. Sample size considerations in clinical trials when comparing two interventions using multiple co-primary binary relative risk contrasts. Statistics in Biopharmaceutical Research 2015; 7:81-94. Abstract

Hamasaki T, Asakura K, Evans SR, Sugimoto T, Sozu T. Group sequential strategies for clinical trials with multiple co-primary endpoints.Statistics in Biopharmaceutical Research 2015; 7:36-54. Abstract

Asakura K, Hamasaki T, Sugimoto T, Hayashi K, Evans SR, Sozu T. Sample size determination in group-sequential clinical trials with two co-primary endpoints. Statistics in Medicine 2014; 33:2897-2913. Abstract

Sugitani T, Hamasaki T, Hamada C. Partition testing in confirmatory adaptive designs with structured objectives. Biometrical Journal 2013; 55:341-59. Abstract

Hamasaki T, Sugimoto T, Evans SR, Sozu T.Sample size determination for clinical trials with co-primary outcomes. Exponential event-times. Pharmaceutical Statistics 2013; 12:28-34. Abstract

Sugimoto T, Sozu T, Hamasaki T, Evans SR.A logrank test-based method for sizing clinical trials with two co-primary time-to-events endpoints. Biostatistics 2013; 14:409-421. Abstract

Sozu T, Sugimoto T, Hamasaki T. Sample size determination in clinical trials with multiple co-primary endpoints including mixed continuous and binary variables. Biometrical Journal 2012; 54:716-729. Abstract

Sugimoto T, Sozu T, Hamasaki T. A convenient formula for sample size calculations in clinical trials with multiple co-primary continuous endpoints. Pharmaceutical Statistics 2012; 11:118-128. Abstract

Sozu T, Sugimoto T, Hamasaki T. Sample size determination in superiority clinical trials with multiple co-primary correlated endpoints. Journal of Biopharmaceutical Statistics 2011; 21:650-668. Absract

Sozu T, Sugimoto T, Hamasaki T. Sample size determination in clinical trials with multiple co-primary binary endpoints. Statistics in Medicine 2010; 29:2169-2179. Abstract

Ando Y, Hamasaki T. Practical issues and lessons learned from multi-regional clinical trials via case examples: A Japanese perspective. Pharmaceutical Statistics 2010; 9:190-200. Abstract

Arano I, Sugimoto T, Hamasaki T, Ohno Y. Practical application of cure mixture model to long-term censored survivor data from a withdrawal clinical trial of patients with major depressive disorder. BMC Medical Research Methodology 2010; 10:33. Abstract

Hamasaki T, Kim SY. Box and Cox power-transformation to confined and censored nonnormal responses in regression. Computational Statistics & Data Analysis 2007; 51:3788-3799. Abstract

Sugimoto T, Hamasaki T. Properties of estimators for baseline hazard functions in a semiparametric cure model. Annals of the Institute of Statistical Mathematics 2006; 58:647-674. Abstract

Goto M, Hamasaki T. Practical issues and observations on the use of foreign clinical data in the drug development. Journal of Biopharmaceutical Statistics 2002; 12:369-384. Abstract

Hamasaki T, Isomura T, Baba M, Goto M. Statistical approach to detecting dose-response relationships. Drug Information Journal 2000; 34:579-590. Abstract

Clinical Trials, and Observational Studies (Selected Papers)

Koga M, Yamamoto H, Inoue M, Asakura K, Aoki J, Hamasaki T, Kanzawa T, Kondo R, Ohtaki M, Itabashi R, Kamiyama K, Iwama T, Nakase T, Yakushiji Y, Igarashi S, Nagakane Y, Takizawa S, Okada Y, Doijiri R, Tsujino A, Ito Y, Ohnishi H, Inoue T, Akagi Y, Hasegawa Y, Shiokawa Y, Sakai N, Osaki M, Uesaka Y, Yoshimura S, Urabe T, Ueda T, Ihara M, Kitazono T, Sasaki M, Oita A, Yoshimura S, Fukuda-Doi M, Miwa K, Kimura K, Minematsu K, Toyoda K.Thrombolysis with alteplase at 0.6 mg/kg for stroke with unknown time of onset: a randomized controlled trial. Stroke 2020; 51:1530–1538.

Miyoshi T, Maeno Y, Hamasaki T, Inamura N, Yasukochi S, Kawataki M, Horigome H, Yoda H, Taketazu M, Nii M, Hagiwara A, Kato H, Shimizu W, Shiraishi I, Sakaguchi H, Ueda K, Katsuragi S, Yamamoto H, Sago H, Ikeda T, on behalf of the Japan Fetal Arrhythmia Group. Antenatal antiarrhythmic treatment for fetal tachyarrhythmias: a prospective multicentre trial. Journal of the American College of Cardiology 2019; 74:874-885 JACC Editor-in-Chief’s Top 100 papers in 2019

Kinoshita T, Yamakawa K, Matsuda H, Yoshikawa Y, Wada D, Hamasaki T, Ono K, Nakamori Y, Fujimi S. The survival benefit of a novel trauma workflow that includes immediate whole-body computed tomography, surgery, and interventional radiology, all in one trauma resuscitation room: A retrospective historical control study. Annals of Surgery 2019; 269:370-376.

Asakura M, Kim J, Asanuma H, Nakama Y, Tsukahara K, Higashino Y, Ishikawa T, Koba S, Tsujimoto M, Himeno H, Maruyama Y, Ookusa T, Yoda S, Suzuki H, Okubo S, Shimizu M, Hashimoto Y, Satake K, Fujino S, Uzui H, Nagai Y, Kohno T, Mizuno S, Nakahama M, Kanaya H, Murohara T, Fukui K, Takase H, Ohte N, Shiono T, Fukunami M, Endo T, Sawada R, Fujii K Takeuchi M, Ikeda S, Mizuno K, Uematsu M, Matsubara T, Yano S, Takahashi J, Ueda K, Kinoshita Y, Tamita K, Hayashi H, Hamasaki T, Kitakaze M, and PPAR investigators. Cardiovascular outcomes in patients with previous myocardial infarction and mild diabetes mellitus following treatment with pioglitazone: Reports of a randomised trial from the Japan working group for the assessment whether pioglitazone protects DM patients against re-infarction (PPAR Study). EClinicalMedicine 2018; 4:10-24.

Nakamura M, Iijima R, Ako J, Shinke T, Okada H, Ito Y, Ando K, Anzai H, Tanaka H, Ueda Y, Takiuchi S, Nishida Y, Ohira H, Kawaguchi K, Kadotani M, Niinuma H, Omiya K, Morita T, Zen K, Yasaka Y, Inoue K, Ishiwata S, Ochiai M, Hamasaki T, Yokoi H on behalf of the NIPPON investigators. Dual antiplatelet therapy for 6 versus 18 months after biodegradable polymer drug eluting stent implantation. Journal of the American College of Cardiology: Cardiovascular Interventions 2017; 10:1189-1198.

Iida O, Nakamura M, Yamauchi Y, Fukunaga M, Yokoi Y, Yokoi H, Soga Y, Zen K, Suematsu N, Inoue N, Suzuki K, Hirano K, Shintani Y, Miyashita Y, Urasawa K , Kitano I, Tsuchiya T, Kawamoto K, Yamaoka T, Uesugi M, Shinke T, Oba Y, Ohura N, Uematsu M, Takahara M, Hamasaki T, Nanto S. 3-year outcomes of the OLIVE Registry, a prospective multi-center study of patients with critical limb ischemia: A prospective, multi-center, three-year follow-up study on endovascular treatment for intra-inguinal vessel in patients with critical limb ischemia Journal of the American College of Cardiology: Cardiovascular Interventions 2015; 8:1493-1502

Wataya-Kaneda M, Tanaka M, Yang L, Yang F, Tsuruta D, Nakamura A, Matsumoto S, Hamasaki T, Tanemura A, Katayama I. Clinical and histologic analysis of the efficacy of topical rapamycin therapy against hypomelanotic macules in tuberous sclerosis complex. Journal of the American Medical Association: Dermatology 2015; 151:722-730.

Yamakawa K, Aihara M, Ogura H, Yuhara H, Hamasaki T, Shimazu T. Recombinant human soluble thrombomodulin in severe sepsis: a systematic review and meta-analysis. Journal of Thrombosis and Haemostasis 2015; 13:508-519.

Mabuchi S, Matsumoto Y, Kawano M, Minami K, Sasano T, Takahashi R, Kuroda H, Hisamatsu T, Kakigano A, Hayashi M, Sawada K, Seo Y, Hamasaki T, Morii E, Kurachi H, Matsuura N, Kimura T. Uterine cervical cancer displaying tumor-related leukocytosis: A distinct clinical entity with radioresistant feature.The Journal of the National Cancer Institute 2014; 106:dju147

Oze T, Hiramatsu N, Yakushijin T, Miyazaki M, Yamada A, Oshita M, Hagiwara H, Mita E, Ito T, Fukui H, Inui Y, Hijioka T, Inada M, Katayama K, Tamura S, Yoshihara H, Inoue A, Imai Y, Hayashi E, Kato M, Miyagi T, Yoshida Y, Tatsumi T, Kasahara A, Hamasaki T, Hayashi N, Takehara T. Significance of post-treatment alpha-fetoprotein levels for hepatocellular carcinoma incidence after interferon therapy. Clinical Gastroenterology and Hepatology 2014; 12:1186-1195.

Matsumoto S, Sakata Y, Nakatani D, Suna S, Usami M, Hara M, Kitamura T, Hamasaki T, Nanto S, Kawahara Y, Komuro I. Circulating p53-responsive microRNAs are predictive Indicators of Heart Failure after acute myocardial infarction. Circulation Research 2013; 113:322-326.

Iida O, Yokoi H, Soga Y, Inoue N, Suzuki K, Yokoi Y, Kawasaki D, Zen K, Urasawa K, Shintani Y, Miyamoto A, Hirano K, Miyashita Y, Tsuchiya T, Shinozaki N, Nakamura M, Isshiki T, Hamasaki T, Nanto S. Cilostazol reduces angiographic restenosis after endovascular therapy for femoropopliteal lesions in the sufficient treatment of peripheral intervention by cilostazol (STOP-IC) study. Circulation 2013; 127:2307-2315.

Iida O, Nakamura M, Yamauchi Y, Miyamoto A, Kawasaki D, Yokoi Y, Yokoi Y, Soga Y, Zen K, Hirano K, Suematsu N, Inoue N, Suzuki K, Shintani Y, Miyashita Y, Urasawa K, Kitano I, Yamaoka T, Murakami T, Uesugi M, Tsuchiya T, Shinke T, Oba Y, Ohura N, Hamasaki T, Nanto S, on behalf of the OLIVE investigators. Endovascular treatment for infrainguinal vessels in patients with critical limb ischemia. OLIVE registry, a prospective, multicenter study in Japan with 12-month Follow-up. Circulation: Cardiovascular Interventions 2013; 6:68-76.

Yamakawa K, Tasaki O, Fukuyama M, Kitayama J, Matsuda H, Nakamori Y, Fujimi S, Ogura H. Kuwagata Y, Hamasaki T, Shimazu T. Assessment of risk factors related to healthcare-associated methicillin-resistant Staphylococcus aureus infection at patient admission to an intensive care unit in Japan. BMC Infectious Diseases 2011; 11:303.

Matsushima A, Tasaki O, Tomono K, Ogura H, Kuwagata Y, Sugimoto H, Hamasaki T. Preemptive contact precautions for intubated patients reduced nosocomial transmission and infection by MRSA in an intensive care unit. Journal of Hospital Infection 2011; 78:97-101.

Yamakawa K, S Fujimi, T Mohri, H Matsuda, Y Nakamori, T Hirose, Tasaki O, Ogura H, Kuwagata Y, Hamasaki T, Shimazu S. Treatment effects of recombinant human soluble thrombomodulin in patients with severe sepsis: a historical control study. Critical Care 2011; 15:R123.

Shimizu K, Ogura H, Hamasaki T, Goto M, Tasaki O, Asahara T, Nomoto K, Morotomi M, Matsushima A, Kuwagata Y, Sugimoto H. Altered gut flora are associated with septic complications and death in critically ill patients with systemic inflammatory response syndrome. Digestive Diseases and Sciences 2011; 56:1171-1177.

Ikuno Y, Jo Y, Hamasaki T, Tano Y. Ocular risk factors for choroidal neovascularization in pathological myopia. Investigative Ophthalmology & Visual Science 2010; 51:3721-3725.

Yokoe M, Okuno R, Hamasaki T, Kurachi Y, Akasawa K, Sakoda S. Opening velocity, a novel parameter, for finger tapping test in patients with Parkinson's disease. Parkinsonism and Related Disorders 2009; 15:440-444.

Kitakaze M, Asakura M, Kim J, Shintani Y, Asanuma H, Hamasaki T, Seguchi O, Myoishi M, Minamino T, Ohara T, Nagai Y, Nanto S, Watanabe K, Fukuzawa S, Hirayama A, Nakamura N, Kimura K, Fujii K, Ishihara M, Saito Y, J-Wind Study Group. Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): Two randomised trials.The Lancet 2007; 370:1483-1493.

Sato T, Nakanishi T, Yamamoto Y, Andersen MP, Ogawa Y, Fukada K, Zhou Z, Aoike F, Sugai F, Nagano S, Hirata S, Ogawa M, Nakano R, Ohi T, Kato T, Nakagawa M, Hamasaki T, Shimizu A, Sakoda S. Rapid disease progression correlates with instability of mutant SOD1 in familial ALS. Neurology 2005; 65:1954-1957.

Sugai T, Yamamoto Y, Miyaguchi K, Zhou Z, Sumi H, Hamasaki T, Goto M, Sakoda S. Benefit of valproic acid in suppressing disease progression of ALS model mice. European Journal of Neuroscience 2004; 20:3178-3183.

Study Reporting, Education and Training, and Other Publications (Selected Papers)

Kaur A, Franco C, McMahan C, Mark M, Schmidt AM, Hamasaki T. Statisticians tell of COVID-19 effects around the world. AMSTAT NEWS 2021; 531(September 2021):42-44 Abstract

Hamasaki T, Bretz F, LaVange LM, Müller P, Pennello, Pinheiro JC. Roles of hypothesis testing, p-values and decision making in biopharmaceutical research. Statistics in Biopharmaceutical Research 2021; 13:1-5 Abstract

Hamasaki T, Bretz F, Cooner F, LaVange LM, Posch M. Statistical challenges in the conduct and management of ongoing clinical trials during the COVID-19 pandemic. Statistics in Biopharmaceutical Research 2020; 12:397-398 Abstract

Yin X, Hamasaki T, Follmann D, Evans SR. OutSMARTing Superbugs. CHANCE 2020; 33(3):22-30 Abstract

Dimairo M, Coates E, Pallmann O, Todd S, Julious SA, Jaki T, Wason J, Mander AP, Weir CJ, König F, Walton MK, Biggs K, Nicholl J, Hamasaki T, Proschan MA, Scott JA, Ando Y, Hind D, Altman DG. The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. BMJ 2020;369:m115 Abstract, Trials 2020; 21:528 Abstract, 

Dimairo M, Coates E, Pallmann O, Todd S, Julious SA, Jaki T, Wason J, Mander AP, Weir CJ, König F, Walton MK, Biggs K, Nicholl J, Hamasaki T, Proschan MA, Scott JA, Ando Y, Hind D, Altman DG. Development of a consensus-driven CONSORT Extension for randomised trials using an adaptive design. BMC Medicine 2018; 16:210. Abstract

Book Chapters, Textbooks (Selected Publications)

Hamasaki T, Wu YJ, Hsiao CF. Multiple endpoints in multiregional clinical trials, Chapter 17, In Simultaneous Global New Drug Development; Multi-Regional Clinical Trials after ICH E17, eds by: Gang Li et al. London, 2021, CRC Press.

Sakamaki K, Sozu T, Hamasaki T. Multiple Comparison Procedures (Taju Hikaku). Tokyo: Asakura Shotan, 2019. (in Japanese)

Hamasaki T, Asakura K, Ochiai T, Evans SR. Group-Sequential Clinical Trials with Multiple Co-Objectives. Cham/Heidelberg/New York: Springer, 2016.

Sozu T, Sugimoto T, Hamasaki T, Evans SR. Sample Size Determination in Clinical Trials with Multiple Endpoints. Cham/Heidelberg/New York: Springer, 2015.

Hamasaki T. Statistical Essene of Clinical Trials (Rinshousiken no Toukeiteki Essene). Osaka: Osaka University Press, 2010. (in Japanese)

Interviews

Interview of Toshi Hamasaki by BIOP Report. ASA Biopharmaceutical Resport 2020; 27(2):20-22.

Episode 60: Toshimitsu Hamasaki. ASA Biopharm's Pocast, December 31, 2018.

 

Complete list avaiable in Google Scholar

Complete list available in PubMed