Researches

1. A. J-PEM:
   DSRU Japan worked as the executive office for two pilot studies of Prescription-Event Monitoring in Japan (J-PEM).
2. J-PEM has been however suspended since 2004.
   (See scientific publications 1-6)
3. B. Case-control study:
   DSRU Japan has worked as a study office of a case-control study on the association between NSAIDs and upper gastrointestinal bleeding conducted between 2002 and 2005.
   (See scientific publication 7)
4. C. Research on the background incidence of possible adverse drug reaction:
   DSRU Japan has worked as a study office of a retrospective cohort study on the background incidence of interstitial lung disease (ILD) in patients with malignant mesothelioma.
5. ILD is known as an adverse reaction to a wide range of anti-neoplastic drugs and other agents occurring in Japan at a rate much higher than that in other countries (including other Asian countries).
6. The research was conducted to know the background in cidence of ILD in Japanese patients with malignant mesothelioma to evaluate possible occurrence of ILD associated with the new antineoplastic agents for treatment of malignant mesothelioma.
   (See scientific publications 8,9)
7. D. Japan Statin Study (JSS):
   DSRU Japan has been working as a study office of the study called as Japan Statin Study (JSS) conducted as a joint research by Japanese Society for Pharmacoepidemiology (JSPE) and Japanese Society of Hospital Pharmacists (JSHP).
8. The study is to compare the safety profiles of 6 statins available in Japan.
9. The study was initiated in 2008 and the final results were reported in 2014.
   (See scientific publication 10,11)
10. E. Database Study (Japan):
    DSRU Japan has conducted database studies in Japan. Several databases became available in early 2000s. In 2011, the MHLW has started the provision of health care claims data (Japanese National Database, NDB) on a trial basis.
11. DSRU Japan has been involved in the study using NDB data.DSRU Japan has conducted database studies in Japan. Several databases became available in early 2000s.
12. In 2011, the MHLW has started the provision of health care claims data (Japanese National Database, NDB) on a trial basis. DSRU Japan has been involved in the study using NDB data.
    (See scientific publications 12-16)
13. F. Database Study (International):
    DSRU Japan has been also involved in the database study using databases available in Japan in collaboration with researchers in ‘Special Interest Group’ (SIG) called as Asian Pharmacoepidemiology Network (AsPEN) in International Society of Pharmacoepidemiology (ISPE).
    (See scientific publications 17-29).
14. G. Pharmacoepidemiology study design:
    DSRU Japan has been involved in the research on pharmacoepidemiology design. Since 2021, studies on the methods to remove biases unique to case-crossover studies (bias due to within-subject exposure dependency and bias due to lack of pairwise exchangeability) have been conducted and will be continued as a cooperative research with South Australia University.
    (See scientific publications 30-33).

Other activities

1. H. Disproportionality measures from Japanese Spontaneous Reports for signal detection:
   Since 2003, DSRU Japan has provided lists of disproportionality measures (PRR, ROR, GPS and BCPNN) obtained from Japanese spontaneous reports accessible through the Internet to members of NPO DSRU Japan.
   (see scientific publication 34)
2. I. Therapeutic Risk Management:
   DSRU Japan has been working as an executive office of the Safety Management system for Unapproved Drugs (SMUD) by the contract with Ministry of Health, Labour and Welfare (MHLW).
3. Though the system may be used for safety management of unapproved drugs in general in the future, it is currently used to monitor thalidomide imported by physicians.
4. Thalidomide approved in 2008 has been used strictly for treatment of patients with malignant myeloma in Japan and thalidomide is still imported by physicians.
5. SMUD requires physicians to register initials and date of birth, gender, diagnosis of patients for whom thalidomide will be imported.
6. For each registered patient, the executive office sends a brochure with information needed to secure safe use of thalidomide.
7. Doctor is also requested to report serious adverse events using the web system.
   (see scientific publication 35)
8. J. Support for Clinical Researches:
   DSRU Japan supported early 3 ‘investigator initiated clinical researches’ as to handling of safety information in the study around when this ‘investigator initiated clinical research’ was introduced to Japan in 2003.
   (see reference 36)
9. K. Validation study:
   DSRU Japan has been involved in the validation studies on the definition of death, the definition of acute myocardial infarction, and the definition of rheumatoid arthritis for the researches using Japanese claims database.
   (see scientific publication 37-39)
10. L. Support for education and meetings of pharmacoepidemiology:
    DSRU Japan has been supporting 6-month course of ‘Pharmacoepidemiology Seminar’ held by Union of Japanese Scientists and Engineers conducted every year since 2006.
11. DSRU Japan worked as an executive office for the 2nd Asian Conference on Pharmacoepidemiology (ACPE2) in 2007 as well as in the 5th Asian Conference on Pharmacoepidemiology (ACPE5) in 2010.
12. M. Consultation for pharmacoepidemiology studies:
    DSRU Japan has provided opportunities of consultation for those in charge of designing/conducting post-marketing studies in drug companies in Japan.

A. J-PEM

1. 1. Kubota K. A Design for Prescription-Event Monitoring in Japan (J-PEM). Pharmacoepidemiol Drug Saf. 1999;8(6):447–456.  https://doi.org/10.1002/(SICI)1099-1557(199910/11)8:6%3C447::AID-PDS446%3E3.0.CO;2-I
2. 2. Yokotsuka M, Aoyama M, Kubota K. The Use of a Medical Dictionary for Regulatory Activities Terminology (MedDRA) in Prescription-Event Monitoring in Japan(J-PEM). Int J Med Inform. 2000;57:139–153. https://doi.org/10.1016/S1386-5056(00)00062-9
3. 3. Kubota K, Kawabe E, Hinotsu S, Hamada C, Ohashi Y, Kurokawa K. Pilot Study of Prescription-Event Monitoring in Japan (J-PEM) Comparing Troglitazone with Alternative Oral Hypoglycaemics. Eur J Clin Pharmacol. 2001;56:831–838. https://doi.org/10.1007/s002280000232
4. 4. Tanaka K, Morita Y, Kawabe E, Kubota K. Drug Use Investigation (DUI) and Prescription-Event Monitoring in Japan (J-PEM). Pharmacoepidemiol Drug Saf. 2001;10(7):653–658. https://doi.org/10.1002/pds.642
5. 5. Kubota K. Prescription-Event Monitoring in Japan (J-PEM). Drug Saf. 2002;25(6):441–444.  https://doi.org/10.2165/00002018-200225060-00008
6. 6. Samizo K, Kawabe E, Hinotsu S, Sato T, Kageyama S, Hamada C, Ohashi Y, Kubota K. Comparison of losartan with ACE inhibitors and dihydropyridine calcium channel angtagonists. A pilot study of Prescription-Event Monitoring in Japan. Drug Saf. 2002;25(11):811–821. https://doi.org/10.2165/00002018-200225110-00005

B. Case-control study

1. 7. Sakamoto C, Sugano K, Ota S, Sakaki N, Takahashi S, Yoshida Y, Tsukui T, Osawa H, Sakurai Y, Yoshino J, Mizokami Y, Mine T, Arakawa T, Kuwayama H, Saigenji K, Yakabi K, Chiba T, Shimosegawa T, Sheehan JE, Perez-Gutthann S, Yamaguchi T, Kaufman DW, Sato T, Kubota K, Terano A.  Case-control study on the association of upper gastrointestinal bleeding and nonsteroidal anti-inflammatory drugs in Japan. Eur J Clin Pharmacol. 2006;62(9):765–772. https://doi.org/10.1007/s00228-006-0171-6

C. Research on the background incidence of possible adverse drug reaction

1. 8. Nojiri S, Gemba K, Aoe K, Kato K, Yamaguchi T, Sato T, Kubota K, Kishimoto T. Survival and prognostic factors in malignant pleural mesothelioma: a retrospective study of 314 patients in the west part of Japan. Jpn J Clin Oncol. 2011;41(1):32–39. https://doi.org/10.1093/jjco/hyq159
2. 9. Nojiri S, Gemba K, Aoe K, Kato K, Yamaguchi T, Sato T, Kubota K, Kishimoto T. Incidence of interstitial lung disease in patients with mesothelioma in the west part of Japan. Pharmacoepidemiol Drug Saf. 2011;20(6):643–652. https://doi.org/10.1002/pds.2123

D. Japan Statin Study (JSS)

1. 10. Kageyama S, Kitamura M, Kokan A, Kubota K, Matsui K, Ooba N, Orii T, Sato T, Shimodozono Y, Uehara H, Yagame M, Yaju Y, Yamaguchi T. Japan Statin Study (JSS), a prospective case-cohort study for monitoring multiple adverse events: rationale, design and characteristics of study subjects. Pharmacoepidemiol Drug Saf. 2010;19:S169. https://doi.org/10.1002/pds.2019

1. 11. N Ooba, T Sato, A Wakana, T Orii, M Kitamura, A Kokan, H Kurata, Y Shimodozono, K Matsui, H Yoshida, T Yamaguchi, S Kageyama, K Kubota. A Prospective Stratified Case-Cohort Study on Statins and Multiple Adverse Events in Japan. PLOS ONE 9(5):e96919. https://doi.org/10.1371/journal.pone.0096919

E. Database studies in Japan

1. 12. Ooba N, Setoguchi S, Ando T, Sato T, Yamaguchi T, Mochizuki M, Kubota K. Climas-based definition of death in Japanese claims database: validity and implcations. PLOS ONE 2013;8(5):e66116. https://doi.org/10.1371/journal.pone.0066116

1. 13. Kubota K, Kamijima Y, Sato T, Ooba N, Koide D, Iizuka H, Nakagawa H. Epidemiology of psoriasis and palmoplantar pustulosis: a nationwide study using the Japanese national claims database. BMJ Open 2015;5:e006450. https://doi.org/10.1136/bmjopen-2014-006450

14. 14. Ooba N, Setoguchi S, Sato T, Kubota K. Lipid-lowering drugs and risk of new-onset diabetes: a cohort study using Japanese healthcare data linked to clinical data for health screening. BMJ Open 2017;7:e015935. https://doi.org/10.1136/bmjopen-2017-015935

15. 15. Kubota K, Ooba N, Kamijima Y, Sato K, Koide D. The use of anticoagulants in patients with non-valvular atrial fibrillation between 2005 and 2014: A drug utilization study using claims data in Japan. PLoS One. 2018 Sep 5;13(9):e0203380. https://doi.org/10.1371/journal.pone.0203380
16. 16. Ando T, Ooba N, Mochizuki M, Koide D, Kimura K, Lee SL, Setoguchi S, Kubota K. Positive predictive value of ICD-10 codes for acute myocardial infarction in Japan: a validation study at a single center. BMC Health Serv Res. 2018 Nov 26;18(1):895. https://doi.org/10.1186/s12913-018-3727-0

F. Database study (International)

1. 17. Andersen M, Bergman U, Choi NK, Gerhard T, Huang C, Jalbert J, Kimura M, Kimura T, Kubota K, Lai ECC, Ooba N, Ösby U, Park BJ, Pratt N, Roughead EE, Sato T, Setoguchi S, Shin JY, Sundström A, Yang YHK. The Asian Pharmacoepidemiology Network (AsPEN): Promoting multi-national collaboration for pharmacoepidemiologic research in Asia. Pharmacoepidemiol Drug Saf. 2013;22(7):700–704. https://doi.org/10.1002/pds.3439

1. 18. Pratt N, Andersen M, Bergman U, Choi NK, Gerhard Y, Huang C, Kimura M, Kimura T,
   Kubota K, Lai ECC, Ooba N, Ösby U, Park BJ, Sato T, Shin JY, Sundström A, Yang YHK, Roughead EE. Multi-country rapid adverse drug event assessment: The Asian Pharmacoepidemiology Network (AsPEN) antipsychoticand acute hyperglycaemia study. Pharmacoepidemiol Drug Saf. 2013;22(9):915–924. https://doi.org/10.1002/pds.3440

1. 19. Pratt N, Chan EW, Choi NK, Kimura M, Kimura T, Kubota K, Lai EC, Man KK, Ooba N, Park BJ, Sato T, Shin JY, Wong IC, Kao Yang YH, Roughead EE. Prescription sequence symmetry analysis: assessing risk, temporality, and consistency for adverse drug reactions across datasets in five countries. Pharmacoepidemiol Drug Saf. 2015;24(8):858–864. https://doi.org/10.1002/pds.3780

1. 20. Roughead EE, Chan EW, Choi NK, Kimura M, Kimura T, Kubota K, Lai EC, Man KK, Nguyen TA, Ooba N, Park BJ, Sato T, Shin JY, Wang T, Griffiths J, Wong IC, Yang YH, Pratt NL. Variation in Association Between Thiazolidinediones and Heart Failure Across Ethnic Groups: Retrospective analysis of Large Healthcare Claims Databases in Six Countries. Drug Saf. 2015;38(9):823–831. https://doi.org/10.1007/s40264-015-0318-4

1. 21. Lai EC, Man KK, Chaiyakunapruk N, Cheng CL, Chien HC, Chui CS, Dilokthornsakul P, Hardy NC, Hsieh CY, Hsu CY, Kubota K, Lin TC, Liu Y, Park BJ, Pratt N, Roughead EE, Shin JY, Watcharathanakij S, Wen J, Wong IC, Yang YK, Zhang Y, Setoguchi S. Brief Report: Databases in the Asia-Pacific Region: The Potential for a Distributed Network Approach. Epidemiology 2015;26(6):815–820. https://doi.org/10.1097/EDE.0000000000000325

1. 22. Lai ECC, Stang P, Yang YHK, Kubota K, Wong ICK, Setoguchi S. International Multi-database Pharmacoepidemiology: Potentials and Pitfalls. Curr Epidemiol Rep. 2015;2:229–238. https://doi.org/10.1007/s40471-015-0059-z
2. 23. Roughead EE, Chan EW, Choi NK, Griffiths J, Jin XM, Lee J, Kimura M, Kimura , Kubota K, Lai EC, Man KK, Nguyen TA, Ooba N, Park BJ, Sato T, Shin JY, Wang T, Wong IC, Yang YK, Pratt NL. Proton pump inhibitors and risk of Clostridium difficile infection: a multi-country study using sequence symmetry analysis. Expert Opin Drug Saf. 2016 Dec;15(12):1589–1595. https://doi.org/10.1080/14740338.2016.1238071
3. 24. Lai EC, Ryan P, Zhang Y, Schuemie M, Hardy NC, Kamijima Y, Kimura S, Kubota K, Man KK, Cho SY, Park RW, Stang P, Su CC, Wong IC, Kao YY, Setoguchi S. Applying a common data model to Asian databases for multinational pharmacoepidemiologic studies: opportunities and challenges. Clin Epidemiol. 2018 Jul 27;10:875–885. https://doi.org/10.2147/CLEP.S149961
4. 25. Lai EC, Shin JY, Kubota K, Man KKC, Park BJ, Pratt N, Roughead EE, Wong ICK, Kao Yang YH, Setoguchi S.  Comparative safety of NSAIDs for gastrointestinal events in Asia-Pacific populations: A multi-database, international cohort study. Pharmacoepidemiol Drug Saf. 2018 Nov;27(11):1223–1230. https://doi.org/10.1002/pds.4663
5. 26. Raman SR, Man KKC, Bahmanyar S, Berard A, Bilder S, Boukhris T, Bushnell G, Crystal S, Furu K, KaoYang YH, Karlstad Ø, Kieler H, Kubota K, Lai EC, Martikainen JE, Maura G, Moore N, Montero D, Nakamura H, Neumann A, Pate V, Pottegård A, Pratt NL, Roughead EE, Macias Saint-Gerons D, Stürmer T, Su CC, Zoega H, Sturkenbroom MCJM, Chan EW, Coghill D, Ip P, Wong ICK.  Trends in attention-deficit hyperactivity disorder medication use: a retrospective observational study using population-based databases. Lancet Psychiatry. 2018 Oct;5(10):824–835. https://doi.org/10.1016/S2215-0366(18)30293-1
6. 27. Kubota K, Kamijima Y, Kao Yang YH, Kimura S, Chia-Cheng Lai E, Man KKC, Ryan P, Schuemie M, Stang P, Su CC, Wong ICK, Zhang Y, Setoguchi S. Penetration of new antidiabetic medications in East Asian countries and the United States: A cross-national comparative study. PLoS One. 2018 Dec 12;13(12):e0208796. https://doi.org/10.1371/journal.pone.0208796
7. 28. Man KKC, Shao S-C, Chaiyakunapruk N, Dilokthornsakul P, Kubota K, Li J, Ooba N, Pratt N, Pottegard A, Rasmussen L, Roughead EE , Shin J-Y, Su C-C, Wong ICK Yank Y-H K, Lai E C-C. Metabolic events associated with the use of antipsychotics in children, adolescents and young adults: a multinational sequence symmetry study. Eur Child Adolesc Psychiatry. 2020. https://doi.org/10.1007/s00787-020-01674-6
8. 29. Su CC, Chia-Cheng Lai E, Kao Yang YH, Man KKC, Kubota K, Stang P, Schuemie M, Ryan P, Hardy C, Zhang Y, Kimura S, Kamijima Y, Wong ICK, Setoguchi S.　Incidence, prevalence and prescription patterns of antipsychotic medications use in Asia and US: A cross-nation comparison with common data model. J Psychiatr Res. 2020 Dec;131:77–84. https://doi.org/10.1016/j.jpsychires.2020.08.025

G. Pharmacoepidemiology study design

1. 30. Kubota K. Symmetry analysis for monitoring safety of newly marketed drugs. Pharmacoepidemiol Drug Saf. 2016; 25: 349–351. https://doi.org/10.1002/pds.3886
2. 31. Hiroi S, Kubota K, Mishiro I, Femandez JL. Post-marketing surveillance in Japan: potential best way forward. Pharmacoepidemiol Drug Saf. 2017 Apr;26(4):1138–1139. https://doi.org/10.1002/pds.4290
3. 32. Kubota K, Kelly TL, Sato T, Pratt N, Roughead E, Yamaguchi T. A novel weighting method to remove bias from within-subject exposure dependency in case-crossover studies. BMC Med Res Methodol. 2021; 21:214. https://doi.org/10.1186/s12874-021-01408-5
4. 33. Kubota K, Kelly TL. Bias Due to Within-Subject Exposure Dependency With or Without Bias Due to Lack of Pairwise Exchangeability When Exposure Is Chronic in Case-Crossover and Case-Time-Control Studies: A Simulation Study. Am J Epidemiol. 2023;192:1701-1711. https://doi.org/10.1093/aje/kwad104

H. Disproportionality measures for signal detection from Japanese Spontaneous Reports

1. 34. Ooba N, Kubota K. Selected control events and reporting odds ratio in signal detection methodology. Pharmacoepidemiol Drug Saf. 2010;19(11):1159–1165. https://doi.org/10.1002/pds.2014

 I. Therapeutic Risk Management

1. 35. Ooba N, Sato T, Watanabe H, Kubota K. Resolving a Double Standard for Risk Management of Thalidomide: An Evaluation of Two Different Risk Management Programmes in Japan. Drug Saf. 2010;33(1):35–45. https://doi.org/10.2165/11318920-000000000-00000

J. Support for clinical researches

1. 36. Ando K, Ohtsu H, Arakawa Y, Kubota K, Yamaguchi T, Nagase M, Yamada A, Fujita T. Rationale and design of the Eplerenone combination Versus conventional Agents to Lower blood pressure on Urinary Antialbuminuric Treatment Effect (EVALUATE) trial: a double-blinded randomized placebo-controlled trial to evaluate the antialbuminuric effects of an aldosterone blocker in hypertensive patients with albuminuria. Hypertens Res. 2010;33(6):616–621. https://doi.org/10.1038/hr.2010.46

K. Validation study

1. 37. Ooba N, Setoguchi S, Ando T, Sato T, Yamaguchi T, Mochizuki M, Kubota K. Climas-based definition of death in Japanese claims database: validity and implcations. PLOS ONE 2013; 8(5): e66116. https://doi.org/10.1371/journal.pone.0066116
2. 38. Ando T, Ooba N, Mochizuki M, Koide D, Kimura K, Lee SL, Setoguchi S, Kubota K. Positive predictive value of ICD-10 codes for acute myocardial infarction in Japan: a validation study at a single center. BMC Health Serv Res. 2018 Nov 26;18(1):895. https://doi.org/10.1186/s12913-018-3727-0
3. 39. Kubota K, Yoshizawa M, Takahashi S, Fujimura Y, Nomura H, Kohsaka H. The validity of the claims-based definition of rheumatoid arthritis evaluated in 64 hospitals in Japan. BMC Musculoskelet Disord. 2021;22:373.  https://doi.org/10.1186/s12891-021-04259-9