Department of Pharmacoepidemiology
School of Public Health, Kyoto University

1. Aim of Establishing the Department
The Department of Pharmacoepidemiology was newly established in 2000 as the first official department for application and education in this field in Japan. There has been a great social demand for using appropriate drugs, practicing standard treatments and preventing adverse drug reactions. Therefore the mission of the department is to accomplish those social demands.
Pharmacoepidemiology is a natural crossing of scientific paths, including clinical epidemiology and clinical pharmacology. Pharmacoepidemiology can be defined as disease-drug informatics which carries out application of epidemiologic reasoning, methods, and knowledges to the study of the uses and effects (beneficial and adverse) of drugs in human populations including clinical trials to　improve outcomes of diseases.
2. Faculty
Professor

Masanori Fukushima, MD, PhD (Kyoto Univ.)
　　Specialty: 1.Medical Oncology 2.Design & Management of Clinical Trial
Associate Professor

Shigeyuki Matsui, PhD (Tokyo University of Science)
　　Specialty: 1. Biostatistics 2. Design and analysis of clinical trial
Secretary Kana Nishisaka
Graduate Students Harue Tada, MPH, RN
Shinzo Hiroi, Pharmacist
Naomi Yokoyama
Naomi Sugiyama
Tsutomu Nishimura
3. Teaching Activities
This section is responsible for instruction in pharmacoepidemiology and design and analysis of clinical trials to graduate students.
Pharmacoepidemiology
Contents
Understanding purpose, method and role of Pharmacoepidemiology
Goal
Picking up the problem through development to dispensing of drugs and planning the approach to solve it.
Educational method
Systematic review of general pharmacoepidemiological methodology
Group study, interactive discussion between lecturers and students
Debate on special medical topic
　　Withdrawal of oral antihyperglycemic agent, pioglitazon (in 2000)
　　Warning of the cancer risk of simvastatin (in 2001)
Textbook
Hartzema, A.C. et al ed. Pharmacoepidemiology: An Introduction 3rd ed., Harvey Whitney. 1998.
Design and analysis in clinical trials
Contents
Design and analysis of clinical trials. Development of protocol. Data management. Critical evaluation of clinical trial papers.
Goal
Being able to write a protocol of clinical studies and to perform statistical analysis.
Educational method
Systematic review of general methodology for clinical trials.
Special lecture on recent topics relating to clinical trials.
Tour of CRO(Contracted Research Organization), pharmaceutical industry and new drug trial operation office in university hospital
Practice of SAS(Statistical Analysis System) using note PC
Presentation
Critical appraisal for clinical trial articles
Textbook
Spilker B., Ed. Guide to Clinical Trials, Raven Press 1991
4. Research Activities
The current research activities are mainly focused on clinical application of pharmacoepidemiological methodologies.
The general research subjects undertaken include:
  1. Developing a new methodology for pharmacoepidemiology and its application.
  2. Risk management for adverse drug effect after marketing.
  3. Planning a epidemiologic study for monitoring adverse events on a new drug.
    4.
  4. Designing clinical trials for new treatments and analyzing their results.
    5.
  5. Biostatistical consultation for biological experiments and clinical researches.
    6.
  6. Developing a new biostatistical methodology.
    7.
  7. Developing a new IT(Information Technology) to support clinical trials.
    8.
The individual research subjects:
  1. Projection of the number of patients with Creutzfeldt-Jakob disease from cadaveric dura transplantation in Japan
    2.
  2. A Cost-Effectiveness and safety evaluation of new combination chemotherapy in non-small cell lung cancer patients
    3.
  3. Influenza-associated encephalopathy in Japan. Statistical analysis for possible association with NSAIDs
    4.
This department also contributed on the society to warn the signal of the drug disaster and to improve medically important regulatory decision-making.
  1. Improvement for the description of the side effect of oral antihyperglycemic agent, pioglitazon in the package insert
  2. Prohibition of NSAIDs with children for antipyretic use
  3. Prohibition of NSAIDs with children for antipyretic use
  4. Proposal for a countermeasure of BSE(Bovine Spongiform Encephalopathy) and vCJD (variant Creutzfeldt-Jakob disease) in Japan

5. Publications
  1. Matsuura, H., Schuller, D.E., Fukushima, M. and Coltman, C.A. Summary of the proceedings of the United States and Japan Head and Neck Cancer Clinical Trials
    Summit, 19-20 September 1997, Kyoto, Japan. J Cancer Res Clin Oncol 125:433-438, 1999.
    2.
  2. Hayakawa, T., Naruse, S., Kitagawa, M., Ishiguro, H., Kondo, T., Kurimoto, K.,Fukushima, M., Takayama, T., Horiguchi, Y., Kuno, N., Noda, A. and Furukawa, T. A prospective multicenter trial evaluating diagnostic validity of multivariate analysis and individual serum marker in differential diagnosis of pancreatic cancer from benign pancreatic diseases. Int. J Pancreatology 25(1):23-29, 1999.
    3.
  3. Sasaki, H., Niimi, S., Akiyama, M., Tanaka, T., Hazato, A., Kurozumi, S., Fukushima, S. and Fukushima, M. Antitumor activity of 13,14-dihydro-15-deoxy-Δ7-PGA1-methyl ester integrated into lipid microspheres against human ovarian carcinoma cells resistant to cisplatin. Cancer Res 59:3919-3922, 1999.
    4.
  4. Leigh, B.R., Gandara, D.R., Crowley, J.J., Furuse, K., Livingston, R.B., Fukushima, M. and Coltman, C.A. Summary of the proceedings of the United States-Japan Lung Cancer Clinical Trials Summit: San Francisco, Califormia, 20-22 November, 1998. Lung Cancer 24:181-191, 1999.
    5.
  5. Fukushima, S., Kishimoto, S., Takeuchi, Y., Fukushima, M. Preparation and evaluation of o/w type emulsions containing antitumor prostaglandin. Advanced Drug Delivery Reviews. 2000, 45:65-75.
    6.
  6. Fukushima, S., Takeuchi, Y., Kishimoto, S., Yamashita, S., Uetsuki, K., Shirakawa, S., Sawada, J., Kojima, M., Suzuki, M., Futsuta, K., Noyori, R., Sasaki, H., Kikuchi, Y., Kita, T., Yamori, Y., Hazato, A., Kurozumi, S., Fukushima, M. Antitumor Activity, Optimum Administration Method and Pharmakinetics of 13,14-Dihydro-15-deoxy-Δ７-prostaglandinA1 methy1 ester (TEI-9826) Intergrated in Lipid Microspheres (Lipo TEI-9826). Anti-Cancer Drugs. 2001,12: 221-234.
    7.
  7. Fukushima, M., Kataoka, T., Hamada, C., Matsumoto, M. Evidence of qi-going energy and its biological effect on the enhancement of the phagocytic activity of human polymorphonuclear leukocytes. American Journal of Chinease Medicine. , 29(1): 1-16,2001.
    8.
  8. Mohri, K., Fukushima, M., Matsumoto, M. Gradual decrease of electric resistivity in water triggered by milli-gauss low frequency plused magnetic field. Transactions of Magnetics Society of Japan. , 1(1),22-26; 2001.
    9.
  9. Toshimitsu Ishida and Chikuma Hamada et al. New DNA polymorphism of human MMH/OGG1 gene: prevalence of one polymorphism among lung-adenocarcinoma patients in Japanese. International Journal of Cancer,80,18-21,1999.
    10.
  10. Hiroyuki Morita,Hiroki Kurihara,Takao Sugiyama Chikuma Hamada,Yukiko Kurihara,Takayuki Shindo,Yoshio Oh-hashi and Yoshio Yazaki. Polymorphism of the methionine synthase gene association with homocysteine metabolism and late-onset vascular diseases in the Japanese population. Arteriosclerosis,Thrombosis and Vascular Biology,19,298-302, 1999.
    11.
  11. Ikuo Nagashima,Teruaki Oka,Chikuma Hamada,Katsutoshi Naruse,Takuya Osada and Tetsuichiro Muto. Histopathological prognostic factors influencing long-term prognosis after surgical resection for hepatic metastases from colorectal cancer. The American Journal of Gastroenterology,94-3,739-743, 1999.
    12.
  12. Junichi Sakamoto,Chikuma Hamada,Susumu Kodaira,Hiroaki Nakasato and Yasuo Ohashi. Adjuvant therapy with oral fluoropyrimidines as main chemotherapeutic agents after curative resection for colorectal cancer: individual patient data ｍeta-analysis of randomized trials. Japanese Journal of Clinical Oncology, 29-2,78-86, 1999.
    13.
  13. Manae Kurokawa and Chikuma Hamada et al. Frequency of clonally expanded T cells evaluated by PCR from a single cell. Journal of Immunological Methods,224, 203-208, 1999.
    14.
  14. Yasuyuki Suzuki,Shiroaki Shirato,Misato Adachi and Chikuma Hamada. Risk factors for the progression of treated primary open-angle glaucoma: a mulitvariate life-table analysis. Graefe’s Archive for Clinical and Experimental Ophthalmology,237,463-467, 1999.
    15.
  15. Yasushi Imai,Hiroyuki Morita,Hiroki Kurihara,Takao Sugiyama,Norihiko Kato, Aya Evihara,Chikuma Hamada,Yukiko Kurihara,Takayuki Shindo, Yoshio Oh-hashi and Yoshio Yazaki. Evidence for association between paraoxonase gene polymorphism and atherosclerotic diseases. Atherosclerosis, 149,435-442, 2000.
    16.
  16. Kiyoshi Kubota, Eri Kawabe, Shiro Hinotsu, Chukuma Hamada, Yasuo Ohashi and Kiyoshi Kubota. Pilot study of prescription-event monitoring in Japan comparing troglitazone with alternative oral hyperglycemics. European Journal Clinical Pharmacology,56,831-838, 2001.
    17.
6. Invited lectures
  1. Masanori Fukushima, A Sino-Japan Seminar on Pharmaceutical Development Cancer Therapy, New stage toward Multinational Trial. 2000.7 China.
  2. Masanori Fukushima, M. International Biotechnology Convention& Exhibition. Epidemiology and Trends in Drug Uses Under the National Health Insurance
    System with Controlled Price Setting in Japan.2001,6 USA.
    3.

7. Presentation at International Meeting
  1. Chikuma Hamada, Junichi Sakamoto, Susumu Kodaira, Hiroaki Nakasato and
    Yasuo Ohashi. DIA 6th Annual Biostatistics Meeting in Tokyo. Meta-analysis of randomized trials for colorectal cancer with oral fluoropyrimidines. 2000,8 Japan.
    2.
  2. Naoko Maeda, Harue Tada, Tetsuji Sadaike, Chikuma Hamada and Masanori Fukushima: Influenza-associated encephalopathy in Japan-Subtype of Reye's syndrome? Possible association with NSAIDs. 17th international conference on pharmacoepidemiology. 2001,8 Canada
    3.

8. Future Prospects
Today, developments and approvals for new drugs are strikingly accelerated. In accelerated drug approval program, surrogate endpoints are used to evaluate efficacy. Being ahead of these new medical trends for accelerated drug approval, the systematic PMS is the most important challenge. Therefore, collaborative surveillance by pharmaceutical companies, academia, and regulatory agency is indispensable to prevent serious adverse reactions.
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