Int j pharm med 2007; 21 (5): 331-338

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Drug Development in Japan
Opportunities and Challenges in Drug Development

1 Banyu Pharmaceutical Co. Ltd., Tokyo, Japan2 Japanese Association of Pharmaceutical Medicine, Tokyo, Japan3 Japanese Centre of Pharmaceutical Medicine, Tokyo, Japan As Japan becomes more integrated into the global market, pharmaceutical research and development (R&D) This material is
in the country faces considerable challenges. While global simultaneous drug development including Asian countries has become a common feature for multinational pharmaceutical companies, Japan has also been frequently set aside because of its unique regulatory requirements and provincial clinical trial infrastructure. To counter this, pharmaceutical companies operating in Japan have been working to improve their efficiency. As a the copyright of the
result, a gradual but measurable improvement in the clinical trial environment has been witnessed over the past several years – including a reduction in average study duration. Meanwhile, a tremendous number of improve- ment programmes focussed on the biopharmaceutical industry have been initiated in conjunction with Prime Minister Shinzo Abe’s vision of innovation for Japan.
original publisher.
With this increased scrutiny, significant improvements in regulatory process, clinical trial costs and site performance are anticipated over the next few years. At the same time, efforts to promote the field of pharmaceutical medicine in Japan are ongoing. A number of academic institutions have established education and training programmes in drug development and regulatory science. In addition, collaborative initiatives between academia and industry to set standards and establish qualification for the specialists in drug develop- Unauthorised copying
ment are continuing with the hope that the number of experts in drug development in Japan will increase. It is hoped that, together, these positive trends will revitalise Japan as a leading global player in pharmaceutical R&D and distribution
Japan continues to be ranked as the second largest pharmaceuti- bined with unique local regulatory requirements and variations in cal market in the world. This fact, in combination with increasing the interpretation and implementation of International Conference development complexity, has led drug development investment on Harmonisation of Technical Requirements for Registration of is prohibited.
for the discovery and development of innovative new pharmaceu- Pharmaceuticals for Human Use (ICH) guidelines, has served to tical products to new heights in Japan.[1] However, as Japan becomes more integrated into the global Across Asia, various English-speaking, motivated work forces market, pharmaceutical research and development (R&D) in the are poised and well-suited to meet the needs of drug development country faces considerable challenges. Most global, R&D-based sponsors. To support this, most of the region’s leading specialists pharmaceutical companies now aspire to develop new drugs glob- have received postgraduate medical training in the US or UK.
ally and, where possible, launch simultaneously around the world.
Since per-subject trial costs are significantly lower in some Asian Under these circumstances, multinational clinical trials have be- countries than they are in Japan, overall cost savings by including come common and the number of trials that include an Asian nonJapanese Asian countries in global clinical trials promise to be country besides Japan has grown rapidly in recent years.[2] A substantial. For example, one report says that the average per- provincial and rather inflexible clinical trial infrastructure, com- subject trial cost in Japan was more than $US20 000, whereas the equivalent cost in Korea and Taiwan was less than $US10 000.[5] come under criticism because of its slow review process. This is At the same time, positive changes in the regulatory climates partly due to the backlog of NDAs that accumulated during the combined with continuous and faster improvements to the clinical merger process. However, the PMDA has recently begun to trial environment under strong government leadership occurred in demonstrate signs of improvement; the backlog of NDAs has been nonJapanese Asian countries than in Japan have allowed smoother dramatically reduced over the past year. Meanwhile, to the ap- and earlier market access for new drugs in these countries.[6,7] plause of long-time experts on the Japanese pharmaceutical indus- With this trend, other Asian countries have made a concerted try, the PMDA has started to encourage Japanese participation in effort to support global clinical trials and have surpassed Japan’s global and Asian regional studies, as well as to accept global and clinical trial performance. Korea has, for example, developed Asian data as core data in NDAs.[12] RENAAL (Reduction of several very strong clinical sites with best-in-class performance in Endpoints in NIDDM with the Angiotensin II Antagonist areas such as number of enrolled patients per trial and number of Losartan) and Tolterodine Japan-Korea studies were the first mul- global protocols. As a result, several significant initiatives to tinational and Asian studies, respectively, to be accepted as core NDA data – with both NDAs approved in April 2006.[13-15] transform and globalise the Japanese pharmaceutical industry have been under serious discussion in Japan.
In addition, the PMDA is committed to hiring 236 new review- This material is
In this article, the current issues and recent changes influencing ers to reach a total of 582 employees by March 2010 with the aim Japan’s clinical trial landscape are reviewed, and the unique of improving the current shortage of reviewers.[16,17] It is also opportunities and future vision for the country’s pharmaceutical working hard to become more of a partner than an adversary to NDA applicants by helping them find the best solutions to meet the copyright of the
regulatory requirements for the approval of new drugs and to 1. Recent Changes in the Regulatory and Clinical establish a transparent and scientific regulatory process.[18] Meanwhile, in support of Prime Minister Abe’s vision, the Ministry of Education, Culture, Sports, Science and Technology original publisher.
(MEXT) and the Ministry of Economy, Trade and Industry (METI) also appear to be strongly interested in improving the Over the course of the last 9 months, the Japanese Prime clinical trial environment. This is evidenced by the fact that the Minister Shinzo Abe has emphasised that the biopharmaceutical MEXT is jointly leading the New 5-Year Plan for Clinical Trial Unauthorised copying
industry is the highest priority focus in his ‘Innovation 25’ vision Activation (2007–2012)[9] with the MHLW, and that MEXT, to- for the next 10 years (originally announced on 29 September gether with MHLW and METI, is playing an important role as a 2006).[8] In accordance with this direction, the Japanese Cabinet, member of the Government-Industry Dialogue for Development of Innovative Medicine, which was initiated in April 2007.[19] in partnership with various government Ministries, is now under- and distribution
taking multiple initiatives to dramatically improve the country’s stagnant regulatory and clinical trial environment.
The Japanese Ministry of Health, Labour and Welfare (MHLW), the agency primarily responsible for pharmaceutical Since the implementation of ICH guidelines, especially E5 is prohibited.
policy, is leading multiple initiatives to promote improvements in (Ethnic Factors in the Acceptability of Foreign Clinical Data)[20] the pharmaceutical environment. These include the New 5-Year and E6 (the consolidated guidelines on Good Clinical Practice Plan for Clinical Trial Activation (2007–2012),[9] the Vision for [GCP])[21] in 1998 and 1997, respectively, many research experts the Pharmaceutical Industry,[10] and the Vision to Improve the acknowledge that the clinical trial environment in Japan has grad- Environment for Vaccines Research, Development and Production ually but measurably improved. In addition to the recent govern- ment initiatives described in the previous section, pharmaceutical As a result of previous improvements, the Pharmaceutical and companies are, on their own initiative, investing resources and Medical Device Agency (PMDA), which is responsible for the money to improve efficiency in clinical trials and to reduce the gap review of New Drug Applications (NDAs) in Japan, was formed in in trial efficiency between Japan and the rest of the world. As one 2003 through the merger of the Pharmaceuticals and Medical example, a 2006 survey conducted by a group of pharmaceutical Devices Evaluation Center and the Organization for Pharmaceuti- companies in Japan demonstrated that the average duration of cal Safety and Research. Following its formation, the PMDA has clinical trials has declined while the use of Clinical Research  2007 Adis Data Information BV. All rights reserved.
Coordinators (CRC) and the number of patients enrolled per site These payment issues originate from Japanese historical and cultural practices that were formalised into the rules when the Based on changes in the clinical trial environment such as those guidelines were first written. As such, it is not easy to solve these outlined previously, many pharmaceutical companies in Japan are issues. Various discussions are ongoing to form a more transparent now conducting – or planning to conduct – an increasing number payment system to improve costs; however, one key driver of cost of global and Asian regional studies. As a result, PMDA officials have announced that the number of consultations regarding global/ Asian studies is increasing.[15] In addition, the PMDA and MHLW 1.3.2 Low Productivity of Field Monitoring have recently circulated A Draft Basic of Policy on International The lower number of clinical trial sites handled by an average Collaborative Clinical Trials for Public Comment, and it is now field monitor in Japan has been recognised as a significant issue. It under revision based on these comments.[22] This guidance will is reported that a field monitor in Japan is in charge of six sites (40 facilitate the conduct of multinational and Asian regional studies subjects) on average, whereas the figures are 22.5 sites (180 subjects) per monitor in the US, and 16 sites (96 subjects) per To conduct multinational trials successfully – and to include a monitor in the EU.[25] This is a major contributor to the high This material is
Japanese cohort – a well designed development strategy is crucial.
manpower costs, and subsequently higher costs in general, associ- There have been a variety of efforts to integrate and align drug ated with performing clinical trials in Japan.
development in Japan with the timelines for global simultaneous In order to improve monitoring productivity in Japan, several development. For example, many companies conduct their first issues need to be resolved. These can only be mitigated through the copyright of the
studies with Japanese subjects outside Japan – in places such as the collaboration between trial sponsors and the trial sites, as well as US, Canada or Australia. Also, it has been proposed that multire- through positive changes in the regulatory requirement. Specifi- gional dose response trials might serve as an alternative option to cally, there seem to be five key drivers of inefficiency: running completely parallel or joint programmes for simultaneous 1. the scope of work for field monitoring is considered to be original publisher.
Joint clinical trials with other Asian countries to broader than most other countries, and this requires a larger ensure rapid patient enrolment are becoming an increasingly com- workload for Japanese field monitors. It is generally expected that mon feature of drug development in Japan.
Japanese field monitors give great consideration to investigator and CRCs workload, and provide on site support for trial sites. For Unauthorised copying
1.3 Challenges in the Clinical Trial Environment in Japan example, field monitors are often expected to assist CRCs and investigators perform the complicated study procedures as defined Despite improvements in the clinical trial environment, the at the site. This significantly increases the resources pharmaceuti- high cost of clinical trials, low productivity of field monitoring and cal companies need to dedicate to trials; and distribution
low performance of trial sites remains significant issues in Japan.
2. the level of quality required for monitoring is higher than 1.3.1 High Cost of Clinical Trials necessary, often termed ‘over-quality’. While many of the reasons As already described in the previous section, it is well docu- behind this (and issue 1) are historical and cultural, creative mented that the cost of drug development is very high in Japan solutions are needed to rationalise these practices; is prohibited.
compared with other Asian countries. The costs vary depending on 3. the workload for documentation is significant. Usually 100% therapeutic areas, company operations and how the costs are monitoring of worksheets and CRFs are expected, and the number calculated. The most recent data available show that the average of essential documents that need to be maintained during the per-subject costs of a clinical trial in Japan are between 3.3- and clinical trial (as required by Japanese GCP) is reported to be 5.6-times higher than those in other Asian countries.[24] excessive and the handling cumbersome;[9] The causes of this high cost are multiple and complicated.
4. various elements of the clinical trial system are also inefficient.
Several issues have been identified as possible causes, including:[5] For example, it has been pointed out that utilising a centralised • payments to nonperforming investigational sites; institutional review board (IRB) system would provide more effi- • inconsistent cost calculation among sites by using ‘point tables cient review by more experienced boards. This would benefit patient safety, especially at smaller private clinics or inexperi- enced trial sites, and would improve field monitoring productivi- • no reimbursement of pre-paid costs to the underperforming ty.[15] Not surprisingly, the more flexible use of centralised IRBs  2007 Adis Data Information BV. All rights reserved.
was proposed in the discussion of networking core clinical trial In addition to transforming Japan’s clinical trial infrastructure, centres in the MHLW’s New 5-Year Plan for Clinical Trial it will be important for companies to undertake novel trial de- signs[28] to optimise Japan’s participation in global and Asian trials. The introduction of emerging new technologies such as 1.3.3 Low Performance of Trial Sites EDC will further reduce cost, accelerate drug development and Improvement in the performance of clinical trial sites is one of increase productivity. For example, the use of EDC in clinical the key factors for the future of drug development in Japan. The trials has been increasing rapidly in the country,[29] and a variety of Pharmaceutical Research and Manufacturers of America’s innovative options for new technologies in clinical trials are ex- (PhRMA) Japan Clinical Trial Environment team conducted a site pected to become available in the near future.
performance survey on the 75 sites that were considered to be the best sites in Japan (as designated by the 14 participating compa- 2. Clinical Trial Specialists and Reviewers nies).[26] The results demonstrated that several positive key prac- tices are present at these sites, including experience with electronic Continuous increase of clinical trial standards demands higher data capture (EDC), participation in global clinical trials and levels of expertise in the drug development arena. Shortfalls in the This material is
English language capability. However, some factors, including the number of clinical trial specialists and reviewers have been identi- enrolment of only a small number of patients per site and the slow fied as an important issue in many countries,[30] including Japan.
administrative procedures, were identified as areas that need sig- Not surprisingly, this is another key aspect that needs improve- ment in Japan’s clinical trial environment – to develop people with the copyright of the
Transforming these ‘best’ trial sites into ‘Centres of Excel- expertise in global drug development.
lence’ would be an important step towards dramatically improving overall clinical trial performance in Japan.
2.1 Drug Development Education and Training An increasing number of universities and regional core hospi- original publisher.
tals have launched clinical trial centres in their facilities – either Various opportunities and methods exist to develop the exper- under their own initiative or through support from the MHLW.[19] tise needed to execute an effective drug development project.
This trend is still at a very early stage; however, significant Unfortunately, such programmes and courses are rather isolated improvements in the clinical trial performance in the areas includ- and efforts are segmented. No clear criteria exist regarding the Unauthorised copying
ing patient enrolment and administrative processes in the near level of knowledge, skills and experience required for individuals future are anticipated because of the enthusiasm observed at many to be recognised as ‘experts’ in the field of drug development and/ of these sites. Similar initiatives have already been instituted in or to become high-quality reviewers. This lack of clear criteria other Asian countries. In Korea, for example, nine institutions could lead to inconsistencies in the quality of clinical trials and the and distribution
have been identified as Centres of Excellence and the number of evaluation of clinical trial results from those studies.
clinical trials, including multinational trials, being undertaken at In order to develop experts in drug development in industry, these centres has dramatically increased.[21] academia and regulatory agencies – that is, those who are capable To be able to conduct clinical trials even more efficiently in the of leading high quality drug development with scientific and is prohibited.
future, it is important to form clinical trial networks by placing regulatory rigor – a well established education and training system these Centres of Excellence as the hub and linking them to other involving a wide scope of drug development is essential. Fortu- research institutions. In addition, collaboration among these cen- nately, an increasing number of initiatives to establish these educa- tres themselves, as well as partnerships with other Asian Centre of tion/training courses are ongoing at this time.
Excellence sites, will be critically important to conduct large pan- In regard to regulators, the PMDA has recognised the need for Asian clinical trials with rapid patient enrolment.
training to produce high-quality reviewers, as it plans to hire The Center for Clinical Trials of the Japan Medical Association additional reviewers over the next 3 years, who may not have (JMACCT) is undertaking the Large-Scale Clinical Trial Network enough experience to review the data for drug development. As a (LCN) Project. This was launched in October 2003, to create a result, the PMDA is committed to implementing a new, compre- country-wide clinical trial network.[27] This project also aims to hensive programme including technical training, on-the-job train- help trial sites gain clinical trial knowledge and skills, including ing, communication and language training[16] in the second half of 2007, and to send the reviewers to workshops and conferences to  2007 Adis Data Information BV. All rights reserved.
help them gain expertise on a par with their European and US and education in pharmaceutical medicine. Much of this work focuses on coordinating and harmonising the existing opportuni- For industry, the Japanese Association of Pharmaceutical ties available in Japan. To date, several Japanese institutions have Medicine (JAPhMed), a group of physicians mostly working in the initiated educational programmes or training courses for drug pharmaceutical industry, has been undertaking activities to estab- development and clinical research (as shown in table II).
lish an education/training system for pharmaceutical medicine.
Given the global and cross-professional aspects of pharmaceu- The outline of the JAPhMed programme is shown in table I.
tical medicine, the harmonisation of the various related program- Training and lectures are given by experienced senior JAPhMed mes is critical to ensure a consistency of quality to global stan- members and/or invited speakers who are experts in each field.
dards. In 2001, the Council for Education in Pharmaceutical Currently, training modules are provided only to members of the Medicine (CEPM) was created under the auspices of the Interna- tional Federation of Associations of Pharmaceutical Physicians Training for academia is described in more detail in the follow- (IFAPP), and undertook the task of harmonising the existing ing sections; some academic institutions have established educa- postgraduate courses in pharmaceutical medicine.[34] JAPhMed is tional courses in the field of drug development and regulatory also working to align its own educational programme with the This material is
2.2 Pharmaceutical Medicine as a Solution the copyright of the
Pharmaceutical medicine is a medical scientific specialty cov- ering the discovery, development, evaluation, registration, moni- toring and medical aspects of the marketing of medicines for the JAPhMed, in collaboration with the R&D Heads Club (an benefit of patients and public health – as defined by the Faculty of industry group that includes 20 domestic and multinational phar- original publisher.
Pharmaceutical Medicine of the Royal College of Physicians of maceutical companies operating in Japan), has founded the Japa- the UK.[33] This breadth of disciplines has been an important nese Center of Pharmaceutical Medicine (JCPM), a nonprofit contributor to the development of consistent quality of clinical organisation, to help advance pharmaceutical medicine for broader trial specialists and reviewers in both the EU and US.
professionals including physicians, pharmacists, nurses and other Unauthorised copying
JAPhMed has been working with a number of Japanese institu- medical staff in academia, industry and regulatory agencies in tions to assist in developing appropriate programmes for training Japan. JCPM has the following specific objectives: • to promote pharmaceutical medicine as a specialty in medical Table I. Outline of pharmaceutical medicine programme proposed by the
science in order to achieve broader recognition of its impor- Japanese Association of Pharmaceutical Medicine Scope of the programme
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tance among industry, academic and government stakeholders; • to develop and expand pharmaceutical medicine training Accreditation system compatible with the Council for Education in programmes – in collaboration with JAPhMed – broadly to those who need to develop drug development expertise; and is prohibited.
Appraisal of the qualification by an external accredited body • to set standards in Japan for pharmaceutical medicine special- Structured continuing education throughout a pharmaceutical physician’s ists and establish qualification for such specialists.
It is hoped that the activities of JCPM will serve to increase the number of local drug development experts in Japan. This organisa- Programme content
tion should also help to improve and maintain the quality of drug development as well as the transparent evaluation of trial results.
Principally covers the core curriculum of the IFAPP syllabus in Figure 1 shows the overall structure of the pharmaceutical Suitable for entry class investigators who will conduct clinical trials medicine education/training system, which JCPM is championing.
Establishing a qualification for pharmaceutical medicine profes- Workshop with case studies by the trainers with practical experiences sionals will significantly improve Japan’s standards for drug de- IFAPP = International Federation of Associations of Pharmaceutical
velopment. In addition, this will greatly facilitate the employabili-  2007 Adis Data Information BV. All rights reserved.
Table II. Academic programmes for drug development and clinical research
Name of the department, programme, or course Laboratory of Pharmaceutical Regulatory Science in Graduate School of Pharmaceutical Division of Pharmaceutical Medicine in School of Pharmaceutical Sciences Department of Pharmaceutical Medicine in Faculty of Medicine Diploma Course on Research & Development of Products to Meet Public Health Needs in Institute of Department of Clinical Trial Management, Graduate School Master’s Programme in Health and Master of Clinical Research in School of Public Health Clinical Research Leadership Development Program nese market simultaneously with the rest of the world with solid This material is
Japanese clinical data produced from cost efficient and scientifi- One of the top priorities of the pharmaceutical industry in Japan cally rigorous clinical trials. This is quite a challenging situation should be to expand the value that the industry provides to the for Japan, and poses a unique opportunity for the industry and future of Japan. This should be in the form of providing break- the copyright of the
through drugs to Japanese patients at the same time as they are provided to patients around the world and, in so doing, adding to To achieve this goal, globalisation of pharmaceutical R&D in Japan is absolutely imperative, and dramatic changes in many The regulatory requirements for collecting Japanese clinical areas must be implemented. These include: original publisher.
data for the approval of new drugs are certainly a burden for • establishing a transparent and scientific regulatory process with pharmaceutical companies. In fact, it is the primary cause of the open and collaborative communication between regulators and ‘drug lag’ in Japan. On the other hand, the availability of Japanese clinical data appear to be quite valuable for practicing physicians Unauthorised copying
• attaining significant improvement in the country’s clinical trial in the country and is advantageous from a Japanese marketing infrastructure and establishing networks of clinical trial sites; point of view as well. Therefore, an ideal scenario for Japan over the next 10 years would be for the pharmaceutical R&D industry • encouraging clinical trial centres to become true ‘Centres of operating in the country to deliver innovative drugs for the Japa- and distribution
Graduate students + company employees + physicians is prohibited.
Examination for qualification executed by JCPM Qualified pharmaceutical medicine professional Fig. 1. Proposed structure for pharmaceutical medicine in Japan by the Japanese Center of Pharmaceutical Medicine (JCPM). There are three ways of
obtaining a professional qualification in pharmaceutical medicine. Academia includes the programmes listed in table II. Non-academic training programmes
include the course provided by the Japanese Association of Pharmaceutical Medicine (JAPhMed). On-the-job training (OJT) is actual work-based
experience within the industry, academia and government, for a certain time period.
 2007 Adis Data Information BV. All rights reserved.
9. New 5-yearly clinical trial activation plan [in Japanese; online]. Available from • adopting new methods for effectively conducting global and URL: [Accessed 2007 10. A draft of vision for the pharmaceutical industry [in Japanese; online]. Available • establishing education and training systems for drug develop- from URL: ment, such as pharmaceutical medicine programmes.
Pcm1010& BID=495070080&OBJCD=100495&GROUP= [Accessed 2007 Any of these changes is challenging and requires intensive 11. Vision to improve the environment for vaccines research, development and pro- efforts from all the key players involved in drug development.
duction in Japan [in Japanese; online]. Available from URL: http:// Fortunately, Japan has significant advantages over many other [Accessed 2007 Aug 22] 12. Miyajima A. Role of Japan and Asia in countries in global pharmaceutical countries with its rich resources in life sciences, including a large development. 2006 Symposium of Asia Pacific Economic Conference (APEC) number of world class scientists, technology experts, and ad- Network. 2006 Oct 12 [online]. Available from URL: vanced academic institutions. A true partnership forged among apec2006ph/presen/1012/03.pdf [Accessed 2007 Jul 9] 13. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and these scientific and technological stakeholders, together with gov- cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N ernment agencies and experienced industry experts, will potential- ly boost the rate of change and will, hopefully, revitalise Japan as a 14. de Koning Gans HJ. Revolution in Asian drug development: a Korea and Japan experience. In: Experience of a Japan/Korea regional trial. Fourth Kitasato true leader in pharmaceutical R&D in the Asian region and be- This material is
University-Harvard School of Public Health Symposium [online]. Available from URL:[Accessed 2007 Jul 9] 15. Mori K. Global development: Japanese efforts and views. 2006 Symposium of Asia Pacific Economic Conference (APEC) Network. 2006 Oct 13 [online].
Available from URL: the copyright of the
The author has no conflicts of interest that are directly relevant to the content of this manuscript. No sources of funding were used to assist in the 16. Key items of 2007 PMDA business plan [in Japanese; online]. Available from URL: h190622 siryo3.pdf [Accessed 2007 Aug 22] The author would like to thank Mr Chris Albani for his through review and 17. The minutes from “2006 PMDA business hyougikai” [in Japanese; online]. Availa- valuable advice on this manuscript, and Ms Mieko Hasegawa for her excellent original publisher.
ble from URL: file/h190306gijiroku.pdf [Accessed 2007 Aug 22] Dr Takahashi is the president of the Japanese Association of Pharmaceuti- 18. Uyama Y. Current status and future perspectives of clinical trial consultation and cal Medicine (JAPhMed) and the vice president of the Japanese Centre of NDA review performance. Sixth Kitasato University-Harvard School of PublicHealth Symposium [online]. Available from URL: http://www. pharm.kitasato- 2005.html [Accessed 2007 Unauthorised copying
19. JPMA News Letter 2007; 119 (5) [in Japanese; online]. Available from URL: http:/ / [Accessed 2007 Aug 22] 1. Office of Pharmaceutical Industry Research report. 2005 Nov [in Japanese; online].
20. ICH harmonized tripartite guideline. Ethnic factors in the acceptability of foreign Available from URL: [Ac- clinical data: E5 (R1) [online]. Available from URL: and distribution
media/MEDIA481.pdf [Accessed 2007 Aug 22] 2. Ishibashi K. Office of Pharmaceutical Industry Research news. 2006 Oct 18-21 no.
21. ICH harmonized tripartite guideline. Guideline for good clinical practice: E6 (R1) 21 [in Japanese; online]. Available from URL: [online]. Available from URL: 3. Ebihara A, Takahashi K, Ikemoto F, et al. Clinical pharmacology and clinical trials 22. A draft of basic policy on international collaborative clinical trials for public in Japan. J Mol Med 1996 Aug; 74 (8): 479-86 comment [in Japanese; online]. Available from URL: 4. McCurry J. Japan unveils 5-year plan to boost clinical research. Lancet 2007 Apr is prohibited.
guide/hyougikai/19/h190608gijishidai/file/shiryo8.pdf [Accessed 2007 Aug 5. Shimatani K. International competitiveness of the Japanese clinical trials on cost 23. E5: ethnic factors in the acceptability of foreign clinical data: questions & answers and performance [in Japanese]. Session 1: performance of new drug research (R1) [online]. Available from URL: and development in Japan and its international competitiveness. In: Takeuchi M, Lagakos SW, editors. Development, evaluation and approval of new drugs-partnership between regulatory agencies, industry and academia. Tokyo: Rin- 24. Shimatani K. Clinical trial performance and cost survey [in Japanese]. Session 2-1: Japan’s critical path opportunities – 1. Reforming the clinical trial process for 6. Varawalla N. Conducting clinical trial in Asia. Appl Clin Trial 2006 Jun 1 [online].
trial conduct: environment and infrastructure of clinical research and trials. In: Available from URL: Takeuchi M, Lagakos SW, editors. Japan’s critical path opportunities. Tokyo: cal+Trials/Conducting-Clinical-Trials-in-Asia/ArticleStandard/Article/detail/ 25. Umehara S. Field Monitor’s scope of work is too broad [in Japanese]. Nikkan 7. Gross A, Hirose M. Conducting clinical trials in Asia. Pacific Bridge Medical 2007 Mar [online]. Available from URL: 26. Taniguchi T. Improvement in Japan’s clinical trial environment: a prospective of lications/html/AsiaClinicalTrials2007.htm [Accessed 2007 Jul 9] global companies: are you ready to use Japanese sites for your global clinical 8. Policy Speech by Prime Minister Shinzo Abe to the 165th session of the diet. 2006 trials? Seventh Kitasato University-Harvard School of Public Health Symposi- Sep 29 [online]. Available from URL: ttp:// um [in Japanese; online]. Available from URL: http://www.pharm.kitasato- abespeech/2006/09/29speech_e.html [Accessed 2007 Jul 9]  2007 Adis Data Information BV. All rights reserved.
27. Uchida T, Kobayashi F, Kiko Tanaka K, et al. Promoting clinical trials in Japan.
[online]. Available from URL: Applied Clinical Trials 2007 Mar 1 [online]. Available from URL: http:// 32. Takahashi K. Training of clinical trial specialists and reviewers [in Japanese].
Clinical-Trials-in-Japan/ArticleStandard/Article/detail/410606 [Accessed 2007 Session 4: Review System and Discussion on Good Review Practice (GRP). In: Takeuchi M, Lagakos SW, editors. Global development strategies of new 28. Califf RM. Issues facing clinical trial of the future. J Intern Med 2003; 254: 426-33 drugs: achievement and future direction. Tokyo: Rinsho Hyoka Kankoukai, 29. Sekine E. Survey results: current status of EDC use in Japan. Session 2-1. Japan’s critical path opportunities – 1. Reforming the clinical trial process for trial 33. Summers K. The pharmaceutical physician. In: Burley DM, Clarke JM, Lasagna L, conduct: environmental and infrastructure of clinical research and trials. In: editors. Pharmaceutical medicine. 2nd ed. London: Edward Arnold, 1993: Takahashi M, Lagakos SW, editors. Japan’s critical path opportunities. Tokyo: 34. Postgraduate courses in pharmaceutical medicine in Europe: a pilot survey. Int J 30. Clemens N. Shortfalls of qualified persons in pharmaceutical medicine. IFAPP Pharm Med 2001; 15 (6); 293-9 [online]. Available from URL: http://www.uni- World I 2007 Apr [online]. Available from URL: [Ac- 01_public/pressemitteilungen/PDFs/IFAPPworld_I_2007.pdf [Accessed 2007 31. Mayer A. A window of opportunity: the cooperative efforts of government agen- cies, pharmaceutical manufacturers and academic researchers are helping to Correspondence: Dr Kihito Takahashi, Banyu Pharmaceutical Co., Ltd, Kita- modernize Japan’s drug development climate. Envisage 2007 Jul; 1 (3): e1 nomaru Square, 1-13-12, Kudan-kita, Chiyoda-ku, Tokyo, 102-8667, Japan.
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