目次Table of Contents

日本語 / Japanese ....................................................................................................... 03
English / 英語 .............................................................................................................. 21
別添 / Appendix........................................................................................................ 41

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 20191

2

Comprehensive and collaborative training
on medical innovations
adapted to challenges of clinical trials
in Asian and African countries
日本語 / JAPANESE目次

目次 ......................................................................................................................................................................................

04

序文 ......................................................................................................................................................................................

05

謝辞 ......................................................................................................................................................................................

06

略語一覧 ..............................................................................................................................................................................

07

図表目次 ..............................................................................................................................................................................

08

1.

09

はじめに .......................................................................................................................................................................
1.1 研修概要 .....................................................................................................................................
1.2 研修の目的 .................................................................................................................................
1.3 研修生の背景 .............................................................................................................................

2.

NCGM 内のプログラム ..............................................................................................................................................
2.1
		
		
2.2
2.3
2.4
2.5
2.6

3.

10

臨床研究センター インターナショナルトライアル部（DIT） ............................................... 10
2.1.1 DIT の概要 ............................................................................................................... 10
2.1.2 MRCT のネットワーク構築に向けて ー DIT の研修プランー ........................... 10
国際医療協力局（BIHC） .......................................................................................................... 11細胞調整管理室（CPC） ........................................................................................................... 12
臨床研究センター（CCS） ........................................................................................................ 12
国際感染症センター（DCC） ................................................................................................... 13
バイオバンク ............................................................................................................................. 14

NCGM 外のプログラム ..............................................................................................................................................
3.1
3.2
3.3
3.4
3.5

4.

09
09
09

医薬品医療機器総合機構（PMDA） ........................................................................................
第一三共株式会社 ......................................................................................................................
国立がん研究センター ..............................................................................................................
聖路加国際大学 .........................................................................................................................
東京女子医科大学・早稲田大学連携先端生命医科学研究教育施設（TWIns）.........................

15

15
17
17
17
18

結語 ...............................................................................................................................................................................

19

今後に向けて ....................................................................................................................................................................... 20
別添 ......................................................................................................................................................................................
別添 1
別添 2
別添 3
別添 4
別添 5
		

研修プログラム ポスター ....................................................................................................
スケジュール ........................................................................................................................
成果報告会案内（日本語） ..................................................................................................
成果報告会案内（英語） ......................................................................................................
各国成果報告会発表資料 ....................................................................................................
1. Clinical Trials in DR Congo: Current Situation and Challenges ......................

42
43
44
45
46
46

		

2. Clinical Trials: Current Situation and Challenges in the Philippines ...............

49

		

3. Clinical Trials in Viet Nam: Current Situation and Challenges ........................

54

		

4. Clinical Trials on Public Institutions in Indonesia ...............................................

60

		

5. Clinical Trials: Current Situation and Challenges in Thailand .......................... 65			4Yves Lula Ntamba / Joelle Lumaya Ambis

			Angeline Monica Adalin Arcenas / Mylene Urtula Cornel

			Nguyen Chinh Dai / Ngo Thi Phuong Nhung

			

Anggi Gayatri / Nina Mariana

			Borimas Hanboonkunupakarn / Boonjing Siripaitoon

41

序文

この度国立国際医療研究センター臨床研究センターが主催する 2018 年度連携各国を対象にした MRCT 能力開発プログラム「A program focused on comprehensive and collaborative training on medical innovations adapted tochallenges of clinical trials in Asian and African countries」実施報告書を発行することになりました。
これは、国立国際医療研究センター臨床研究センターに 2016 年に設立されたインターナショナルトライアル部が実施する国際共同臨床研究ネットワーク拠点形成事業の柱の一つとなる「国際共同臨床研究を実践するための人材育成活動」を報告するものです。
国立国際医療研究センター臨床研究センター・インターナショナルトライアル部は、国際共同臨床研究ネットワー
クを通じて、新興・再興感染症、難治性疾患、希少疾患、生活習慣病などにおける新たな診断、予防、治療法を開発し、世界の医療向上に貢献することをミッションとしています。新規医薬品や医療機器、および新規医療技術の開発を取り巻く環境は近年大きく変化し、我が国においても医薬品開発における信頼性の確保、効率化や標準化の中で、国際共同臨床研究実施を可能とする体制整備が求められています。これまで国立国際医療研究センターが海外で行ってきた国際医療協力に、国際共同臨床研究を通じた新規医療技術の開発という新たな役割を加えて、世界各国の患者の方々に新たな医療を届ける所存です。そのためには、各国と連携し、連携各国において国際標準の手順に基づいて国際共同臨床研究を実施しうる人材を育成することが極めて重要な活動と位置付けています。
2018 年度は、国立国際医療研究センターの連携国となっているコンゴ民主共和国、インドネシア、フィリピン、タイ、
ベトナムそれぞれから 2 名ずつ、合計 10 名を選考し、10 日間に渡る医薬品医療機器総合機構（PMDA）、製薬企業（第一三共株式会社）、学術機関（東京女子医科大学・早稲田大学連携先端生命医科学研究教育施設、聖路加国際大学）、そして臨床現場である国立国際医療研究センター、国立がん研究センターでの講義、ディスカッション、施設見学を織り交ぜた研修プログラムを実施しました。研修後半には成果報告会を実施し、一般の方々を含めアカデミア、製薬
会社、CRO などからの多くの方にご参加いただき、各国の現在の臨床試験の状況と課題について共有する良い機会となりました。本活動が今後の連携国との臨床研究実施協力体制の構築の一助になればと願っています。
本活動にご協力いただいた関係各所には謹んで御礼を申し上げたいと存じます。引き続きご指導ご鞭撻のほど何卒よろしくお願い申し上げます。

								2019 年 3 月 20 日								国立国際医療研究センター								臨床研究センター長										

渡邉

裕司			

					
								Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 20195

謝辞

国際共同臨床研究を進める中で国家間の規制の調和や企業との連携、民族差や医療事情の違いなど、越えるべき課
題は山積しています。
「私たちはパートナー各国からのスタッフと協働することで、これらの課題を解決し、国際共同臨床研究を推進し、グローバルヘルスへ貢献していこうと考えています。
」この一文は、国立国際医療研究センター
臨床研究センター・インターナショナルトライアル部のパンフレットに記載してあるものです。国際共同臨床研究を推進していくためには情熱を持ち、それを適切に実施しうる人材の育成が欠かせません。私たちは、2016 年に設置したインターナショナルトライアル部に、コンゴ民主共和国、インドネシア、フィリピン、タイ、そしてベトナムの各国からの人材をスタッフとして登用しています。世界中の新興・再興感染症、希少疾患、難治性疾患などで苦しむ患者の方々に新たな医療を提供することを目的に、この度、彼ら海外スタッフが日本人のスタッフとともに国際臨床研究の担い手を育む 10 日間のプログラムを設計、企画、運営実施し、関係各所にその成果を報告する機会を得ることができました。本研修を実施するにあたり、医薬品医療機器総合機構をはじめ多くの機関や職員の皆様からご支援、ご協力を頂きました。こころよく受け入れて下さった機関やご指導下さった皆様に、この場をお借りしまして謹んで御礼を申し上げます。
【ご支援、ご協力いただいた法人様】
独立行政法人 医薬品医療機器総合機構
第一三共株式会社
国立研究開発法人 国立がん研究センター
学校法人 聖路加国際大学 公衆衛生大学院
東京女子医科大学・早稲田大学連携先端生命医科学研究教育施設
国立研究開発法人 国立国際医療研究センター

国際医療協力局、CPC、臨床研究センター治験管理室、薬剤部、						

国際感染症センター、バイオバンク【研修生派遣元※ 50 音順】

コンゴ民主共和国

University of Kinshasa、Institut National de Recherche Biomédicale

インドネシア

University of Indonesia、Sulianti Saroso Infectious Diseases Hospital

フィリピン

University of the Philippines、St. Luke’s Medical Center

タイ

Mahidol University、Prince of Songkla University

ベトナム

Cho Ray Hospital、Bach Mai Hospital																2019 年 3 月 20 日								国立国際医療研究センター								インターナショナルトライアル部																臨床研究センター

エグゼクティブマネジメント室長

											

6

飯山

達雄

略語一覧

AMED

AMR
APECRHSC
ATC
BIHC
CCS
CPC
CRC
CRO
DB
DCC
DIT
FY
GCP

ICH

Japan Agency for Medical Researchand Development
国立研究開発法人
日本医療研究開発機構
Antimicrobial resistance
薬剤耐性Asia-Pacific Economic Cooperation
Regulatory Harmonization Steering
Committee
アジア太平洋経済協力
規制調和運営委員会
Asia Training Center

IRB
MEXT
MHLW

アジア医薬品・医療機器
トレーニングセンター
Bureau of International Health
Cooperation

MRCT

Center for Clinical Sciences

NCBN

国際医療協力局

MRI

臨床研究センター
Cell Processing Center
細胞調整管理室
Clinical Research Coordinator
治験コーディネーター

NCC
NCGM

Contract Research Organization
開発業務受託機関
Database
データベース
Disease Control and Prevention Center
国際感染症センター
Department of International Trials
インターナショナル トライアル部
Fiscal Year
会計年度
Good Clinical Practice

PDCA
PMDA
(R)EID
SCOT
SOP

医薬品の臨床試験の実施の基準
The International Conference
on Harmonisation of TechnicalRequirements for Registration of
Pharmaceuticals for Human Use
医薬品規制調和国際会議

IEC

INRB

Independent Ethics Committee
独立倫理委員会

TWIns
WG
WHO

Institut National de Recherche
Biomédicale
コンゴ民主共和国にある
国立生物医学研究所
Institutional Review Board
治験審査委員会

Ministry of Education, Culture, Sports,
Science and Technology
文部科学省
Ministry of Health, Labour and Welfare
厚生労働省
Multi-Regional Clinical Trial
国際共同治験
Magnetic Resonance Imaging
磁気共鳴映像法
National Center Biobank Network
ナショナルセンター・
バイオバンク ネットワーク
National Cancer Center Japan
国立がん研究センター

National Center for Global Health andMedicine
国立研究開発法人
国立国際医療研究センター
Plan-Do-Check-Act cycle
PDCA サイクル
Pharmaceuticals and Medical Devices
Agency
独立行政法人医薬品医療機器総合機構(Re)-Emerging infectious disease（再興）新興感染症
Smart Cyber Operating Theater
スマート治療室
Standard operating procedure
標準業務手順書Tokyo Women’s Medical UniversityWaseda University Joint Institution for
Advanced Biomedical Sciences
東京女子医科大学・早稲田大学連携
先端生命医科学研究教育施設
Working Group
ワーキンググループ
World Health Organization
世界保健機関Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 2019

7

図表目次

番号

表題

図1

DIT プレゼンテーション

10

図2

DIT の役割10

図3

各種団体による臨床試験専門家のためのプログラムの紹介

11

図4

研修プログラム内容の例

11

図5

プログラムの開始にあたり、DIT スタッフと

11

図6

BIHC 担当者によるプレゼンテーション

12

図7

CPC にて、医師、担当者と

12

図8

臨床研究センタープレゼンテーション

12

図9

治験専用診察室13

図 10

モニタリング用個室

13

図 11

臨床研究センタープレゼンテーション

13

図 12

隔離しながら患者さんを輸送する車いす

13

図 13

隔離病室内に設置されている分娩台

13

図 14

DCC 医師によるプレゼンテーション

13

図 15

NCBN の組織体制 (NCBN ホームページより )

14

図 16

バイオバンクの検体保管庫

14

図 17

バイオバンク施設にて、担当者と

14

図 18

PMDA にて15

図 19

第一三共株式会社前にて

17

図 20

国立がん研究センター前にて

17

図 21

聖路加国際病院前にて

17

図 22

聖路加国際病院前にて

18

図 23

聖路加国際大学公衆衛生大学院の先生方と

18

図 24

SCOT（Smart Cyber Operating Theater）スマート治療室

18

図 25

TWIns 前にて

18

番号

8

ページ番号

表題

ページ番号

表１

研修生出身国・所属先一覧

09

表２

PMDA-ATC MRCT Seminar プログラム

16

1.

1.

1.1

はじめに ■

はじめに

研修概要

本研修では、アジア・アフリカ各国における治験の実施環境の整備の一環として、5 カ国より 10 名の研修生を迎えました。10 日間の研修プログラムでは、講義やディスカッション、治験実施施設や教育施設、製薬企業等への訪問を通して、日本における治験の実施状況について学びました。
具体的には、アジア医薬品・医療機器トレーニングセンター（PMDA-ATC）主催の MRCT セミナー 2019 の見学を始めとし、臨床試験や医療イノベーションの現況を学ぶ目的で、治験実施施設（NCGM、NCC）や教育施設（TWIns、
聖路加国際大学）、製薬企業（第一三共株式会社）を訪問しました。
また、オープンセミナーでのプレゼンテーションを通じて、研修生より各国の治験の状況と課題についてご紹介する機会を設けました。

1.2

研修の目的

本研修の目的は以下の通りです。
•

医療イノベーションや国際共同試験関連の規制・実施体制・課題を学ぶ•

今後の各国での臨床試験実施体制の整備に寄与する人材を育成する•

国立国際医療研究センターと各施設とのさらなる協力体制へとつなげる

研修生の背景1.3

アジア・アフリカの計 5 カ国 10 施設より、少なくとも 1 件以上の臨床研究の経験のある医師を研修生として迎えました。
表１

研修生出身国・所属先一覧
Country

The Democratic Republicof the Congo
Indonesia

The Philippines

Thailand

VietnamInstitution

Participant Name

University of Kinshasa

Yves Lula Ntamba

Institut National de Recherche Biomédicale

Joelle Lumaya Ambis

University of Indonesia

Anggi Gayatri

Sulianti Saroso Infectious Diseases Hospital

Nina Mariana

University of the Philippines

Angeline Monica Adalin Arcenas

St Luke's Medical Center

Mylene Urtula Cornel

Mahidol University

Borimas Hanboonkunupakarn

Prince of Songkla University

Boonjing Siripaitoon

Cho Ray Hospital

Nguyen Chinh Dai

Bach Mai Hospital

Ngo Thi Phuong Nhung

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 20199

2.

NCGM 内のプログラム

2.1

臨床研究センター

2.1.1

DIT の概要

インターナショナルトライアル部（DIT）

当部署で実施している、国際共同治験のプラットフォーム構築事
業を中心に紹介がありました。国際感染症フォーラムの実施等で産官学の情報交換・連携体制を促進し、国際的な医療課題を解決する
ような共同開発プロジェクトを生み出す工夫とともに、新興国で国際基準や各国規制を遵守して円滑に国際共同治験を実施するため、DIT が実施している支援等について紹介されました。
各国での適切な治験実施環境を構築すべく、キャパシティビル
ディングにも取り組んでおり、本研修も単独で終了するものではな
く、今後の協業に向けて関係づくりをより一層進めて行きたいというメッセージが送られました。
図 1: DIT プレゼンテーション

International coordinating organization for global clinical research
Concept

Capitalizing on the long history and expertise of NCGM in international medical cooperation, we established an
Academic CRO focusing on global health issues, starting with Emerging and Re-emerging Infectious Diseases. The
Department of International Trials network facilitates medical innovation through Multi-Regional Clinical Trials(MRCTs) with counterparts.
Counterpart countries:
Thailand
VietnamPhilippines Indonesia
DR Congo and others
Activities

 Formulate a platform consisting of human resources from network nations to copewith MRCTs (housed at NCGM)
 Establish clinical trial networking, standardized operational procedures, andmutual cooperation with clinical sites in Asia and Africa
 Implement MRCTs in concurrence with priority of WHO/ nations/ sites

NCGM
clinical research center
Inhouse Collaboration in NCGM

Benefits

International Harmonization
PMDA-ATC*APEC-RHSC**

Partnership with
Industries
Consortium

Health & Medical Strategy• Clinical Innovation Network• Contribute to control of (R)EID,
intractable and rare disease• Medical Innovation supported by larger numbers of cases for (R)EID, intractable
and rare diseases• Reinforcement of new drug/medical device development through MRCTs• Contribution to drug-lag minimization and therapeutic optimization in Asian nations• Improvement of health care and medicines in the world
National Center for Global Health and Medicine

図 2: DIT の役割

2.1.2

MRCT のネットワーク構築に向けて -DIT の研修プラン -研修の計画・実施に関して中心的な役割を果たしてきた DIT の研修担当者より、臨床研究と治験の違い、治験実施の必要性、
特に MRCT において必要となる継続的な知識のアップデート、昨今、全世界的に活発化している規制やデータ収集手法の共通化の動き等について確認しました。
その上で、今後 DIT において計画している国際的な治験専門家の育成プログラムの概要を紹介しました。DIT が目指す、
ICH ガイドライン等の国際基準に準じた試験を実施できる人材の育成のため、様々な団体が公表している臨床試験、治験専門家の要件や、トレーニングに必要な要素を参考にしながらプログラムの開発を行っていることを紹介しました。研修生からは

10

2.

NCGM 内のプログラム■

多くの質問が聞かれ、研修生の学ぶ意欲の高さと、治験教育への関心の高さを確認することができました。
さらに、研修生が今後の DIT トレーニングプログラムに期待すること、各研修生が所属する施設における治験の実施状況、
今回のプログラムにおける感想や改善点などについて、活発なディスカッションが行われました。

For Organized program…

Candidate contents

We are developing ourtraining program referring
various global standards
and collaborative activities.

© 2018 National Center for Global Health and Medicine2

図 3: 各種団体による臨床試験専門家のためのプログラムの紹介

Preparation/Principle

Conduct/Procedure

Quality of Trial Data

• Relevant guidelines:
Declaration of Helsinki• Drug development• General considerations forClinical Trials (ICH-E8)• General principles onplanning/designing MultiRegional Clinical Trial (ICHE17)• IRB/IEC• Patient safety andindemnification• Conflict Of Interest (COI)Management• Local Regulations (having
impact for MRCTs)• ICH GCP (E6)• SOP
• Protocol• Investigational ProductManagement• Informed consent• Compliance and issue
reporting• Risk mitigation• Data Entry(Electronic Data
Capture)• Expedited Safety Reporting:
ICH-E2A• Essential documents
Retention (electronic Trial
Master File)• Statistical Principles forClinical Trials(ICH-E9)• Statistical Considerations• Statistical Analysis Plan(SAP)• Data management• Medical Dictionary forRegulatory Activities(MedDRA)• Quality assurance• Risk management Plan
• Monitoring• Sponsor Audit• Regulatory Authority
Inspection• Common TechnicalDocument(CTD)

In addition, Several theme (Performance test for medical device, Specific Regulation in
Japan, Cutting-age Medical Technologies etc…) can be optional materials.
© 2018 National Center for Global Health and Medicine1

図 4: 研修プログラム内容の例

https://mrctcenter.org/clinical-trial-competency/
https://www.diaglobal.org/en
https://acrpnet.org/
https://www.who.int/tdr/publications/year/2016/competencyframework-clinical-res/en/
https://www.transceleratebiopharmainc.com/

図 5: プログラムの開始にあたり、DIT スタッフと

2.2

国際医療協力局（BIHC）

組織の概要や NCGM 内での位置づけ、その機能や約 40 年にも及ぶ国際協力の歴史とともに、技術協力事業と政策提言に関する活動について紹介がありました。
技術協力事業には、公衆衛生、母子保健と家族計画、感染症対策、医療施設の整備といった種類があり、例えば医療施設の整備プロジェクトでは、医療技術移転、医療システムや緊急医療システムの整備、経営や医療機器の管理等
Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201911

を含む病院管理、看護師やその他の医療従事者への教育を含む人的リソースの開発等、医療施設を開設し、維持・管理していくための
包括的な支援を提供していることが紹介されました。
こういった技術協力によって得られた課題や知見をもとに、現場の状況を考慮・反映し、政策への提言・助言を行えることも、国際医療協力局の強みであることが紹介されました。
図 6: BIHC 担当者によるプレゼンテーション

2.3

細胞調整管理室（CPC）

細胞治療は多くの変性疾患、非感染性疾患における革新的な医療となっています。細胞治療を実施するためには、特定の要件を満たした施設で処理、培養された良質な細胞が必要となります。
実際に、CPC の運営や臨床試験に関わる 2 名の医師より、CPC について紹介がありました。
CPC は、厳格に管理されているクリーンルーム
であり、微生物の混入を防いで安全に細胞培養を行うためアイソレーターやクリーンベンチを備えています。施設をモニタリング・コントロールする機器類や、病院の建物自体の空調システムや配管設備との兼ね合いも含め、様々な工夫の下に施設が維持されているとの説明を受けました。

図 7: CPC にて、医師、担当者と1 型糖尿病や慢性膵炎でインスリン治療を行っていても血糖値が不安定な方を対象に、ドナーより提供された膵臓から、膵島細胞のみを分離して移植する膵島移植の臨床試験プロジェクトについても紹介されました。
患者さんの生命維持・生活の質改善に直結する臨床試験プロジェクトの紹介に対し、医師・薬剤師である研修生は大いに興味を持ち、様々な観点から質問が寄せられました。

2.4

臨床研究センター（CCS）

臨床研究センターの組織概要、治験事務局、治験管理室の業務等についての紹介の後、当院で実施している治験のインフォームドコ
ンセントの取得について、プレスクリーニングから患者さんへの治験参加の呼びかけを含む一連のプロセスを追って、治験責任医師、
CRC の果たす役割を含む詳しい説明がありました。
外来エリアに位置する治験専用診察室や、中央検査室、治験関連機器を保管する専用の倉庫の様子も、写真で紹介されました。多数の企業治験を同時に実施していく中で、一貫したデータ取得のため企業等から貸与される様々な機器の管理も、治験の適切な実施にあたり重要なポイントとなることが紹介されました。
治験管理室の訪問では治験関連文書が施錠できるロッカーに格納されている様子や、併設されているモニタリング用の個室を見学しました。モニタリング用の個室では、実際に製薬企業のモニターが12

図 8: 臨床研究センタープレゼンテーション

2.

NCGM 内のプログラム■作業を実施しており、個室でプ
ライバシーを確保しながらモニタリングを実施する様子が見学できました。膨大な量の治験関連文書を保管するにあたり、過去の文書については一部、外部倉庫と契約して適切に保管できるよう工夫しているといったお図 9: 治験専用診察室

図 10: モニタリング用個室

話もありました。
薬剤部と治験薬管理庫の訪問
では、膨大な量の院内処方の調剤を行う薬剤部の中に、アクセス制限付きで、様々な温度管理に対応できる治験薬管理庫を見学しました。温度逸脱時には担当者のメールアドレスに通知が送信され、担当者はスマートフォン等で常に通知を確認できる体制を整えている旨も説明があり
図 11: 臨床研究センタープレゼンテーション

ました。

2.5

国際感染症センター（DCC）

まず始めに、DCC の活動の紹介がありました。
DCC は、薬剤耐性菌を含む感染症の予防、診断、治療と、それらに携わる専門家や医療従事者の育成を行っています。また、感染症の制御や教育における連携・協力のため、国内外を含む様々な機
関とネットワークを形成しています。輸入感染症の早期検出・リス
クアセスメントと迅速な対応に向けた研究者の育成を始めとした、感染症の水際対策への活動も実施しています。
DCC の病棟・病室の見学では、第一類感染症、第二類感染症、
特定感染症の患者さんを受け入れることのできる病室を訪問しました。感染の拡大を防ぐため、患者さんの移動や物品の受け渡しルートが厳格に管理された隔離室は医療者が必要な治療やケアを提供する妨げとならないよう、様々な工夫がみられました。

図 13: 隔離病室内に設置されている分娩台

図 12: 隔離しながら患者さんを輸送する車いす

図 14: DCC 医師によるプレゼンテーション

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 2019

13

2.6

バイオバンクNCGM 単独の施設としてのみならず、NCBN(National Center Biobank Network) の一施設として、ネットワーク内におけるナショナルセンター間での協力体制の構築や、文書や手続き、手順等の統一化、各センターの役割の明確化など、より広範囲なバイオバンクとしての役割や活動について、紹介がありました。
NCBN は国内 6 ナショナルセンターからなるバイオバンクのネットワークであり、収集される検体の種類は各ナショナルセン
ターの専門性によって異なります。利用のための問い合わせ窓口は NCBN 事務局で一括して実施されており、ナショナルセンター
以外に所属する、国内外の企業を含む研究者も検体の利用申請が可能であることも紹介されました。ネットワークを構成する施設間での情報交換や協議によって、より適切な同意の取得、検体の維持管理、利用提供等への取り組みが進められています。
厳格な温度管理の下、検体を保管している施設を見学し、今後も保管検体が増加することを見越した施設設計であるとの紹介がありました。
提供者からの同意取得プロセスには細心の注意が払われており、また個人情報保護の観点から、提供者の情報を共有する際には匿名化を始めとした非常に厳格な管理が行われているとの説明がありました。
本件の問い合わせ先（NCGM バイオバンク）：ncgmbb@hosp.ncgm.go.jp

図 15: NCBN の組織体制

https://ncbiobank.org/organization/index.php

図 16: バイオバンクの検体保管庫

14

図 17: バイオバンク施設にて、担当者と

3.

3.

3.1

NCGM 外のプログラム■

NCGM 外のプログラム

医薬品医療機器総合機構（PMDA）

PMDA と NCGM の包括的連携協定に基づき、PMDA アジア医薬品・医療機器トレーニングセンター（PMDA-ATC）主催の国際共同治験セミナー 2019（MRCT Seminar 2019）のオブザーバーとしての見学の機会を得ました。
本セミナーは日本が今まで培ってきた MRCT の計画・デザイン及び実施、臨床データの評価、GCP 調査結果に基づいた承認審査、国際共同治験に基づき承認された医薬品の市販後ベネフィットリスク評価といった知識・経験を活用し、医薬品開発に関する規制の調和を促進することを目的としており、各国規制当局担当者の参加を対象とするものです。
MRCT の計画・デザイン、実施及び結果の評価における留意点、GCP 調査結果を踏まえた承認審査における留意点、
MRCT に基づき承認された医薬品の市販後安全性評価に至るまで、包括的かつ各専門家のご経験や事例に基づいた詳細な講義を聴講しました。特に、MRCT の実施や GCP 調査、市販後ベネフィットリスク評価、国際連携と整合性に関して、PMDA のみならず、製薬業界やアカデミアの先生方からのご講義を聴講することで、より実務に即した形で
MRCT についての学びを深めることができました。
更に各国規制当局からの参加者より、各国における承認審査の体制や手順の概要、ICH E17 ガイドラインの実装に当たっての課題等が紹介され、DIT 研修生の出身国 5 カ国のみならず、様々な国の医薬品審査・承認制度の概要を知ることできたことは研修生にとって大きな学びとなりました。
■ PMDA-ATC MRCT Seminar 紹介ページ :https://www.pmda.go.jp/english/symposia/0138.html

図 18: PMDA にて
Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 2019

15

表2

PMDA-ATC MRCT Seminar プログラム（PMDA ホームページより、DIT 研修生が参加したプログラムのみ転載 )PMDA-ATC Multi-Regional Clinical Trials (MRCT) Seminar 2019
Offered by Asia Training Center for Pharmaceuticals and Medical Devices Regulatory Affairs
DATE: January 21-24, 2019 / VENUE: PMDA
DAY 1 (January 21, 2019)
Key note speech
Strategies and challenges for drug development- Future movements and backgrounds of development strategies History of drug evaluation using overseas data in Japan Q&A
Scientific insights about ethnic factors Q&A<Session 1>
Introduction of review systems and regulations by participants<Session 2>
International cooperation and alignment•
Global platform for medical innovation as an Academic Research Organization (ARO)
Challenge for global cooperation of regulatory agencies•
Q&A
DAY 2 (January 22, 2019)<Session 3>
Points to consider when planning and designing MRCT
Points of attention for consultation about MRCT from PMDA’s experience•
Case study -Planning and designing MRCT•
Q&A<Session 4>
Points to consider when evaluating results
Statistical considerations for MRCT based on the ICH E17 guideline•
PMDA’s experiences to review MRCT results•
Q&A
DAY 3 (January 23, 2019)<Session 5>
Considerations for MRCT operations
Practical issues and solutions on MRCT operations (Investigator’s viewpoint)••
Practical issues and solutions on MRCT operations (Industry’s viewpoint)
Q&A
DAY 4 (January 24, 2019)<Session 6>
Regulatory review based on results of GCP inspection
How to perform GCP inspection in Japan -Role of GCP inspection in review process••How to take GCP inspection results into consideration for review from reviewer’s perspective•
Applicant’s experiences to undergo GCP inspection
Trial site’s experiences to undergo GCP inspection•
Q&A<Session 7>
Post-market safety evaluation of approved drugs based on MRCT
Global standards for pharmacovigilance•
Risk management plan based on the multi-regional clinical development -from perspectives of pharmaceutical•companiesRisk management based on the multi-regional clinical development - from perspectives of regulatory agencies •
Q&A

16

3.

3.2

NCGM 外のプログラム■

第一三共株式会社

まず始めに、会社の概要とともに新薬開発のプロセスについて説明がありました。特に、薬剤の候補となる物質が臨床試験でその有効性と安全性を確認される段階になる前の過程
で、多くの物質の中からふるいにかけられ、年月をかけてその性質や生体内での働きについて実験を通して確認されるという薬剤開発の基礎の部分について学ぶことができました。
その後は新規医薬品を見出すべく、日々研究が重ねられているラボを見学しました。最新の機器や設備を使用しながら、新薬の開発に向けて研究がおこなわれている現場を見ることができました。

図 19: 第一三共株式会社前にて研究所には、本製薬会社で開発され、世界中で販売されている医薬品の化学構造体模型と、各薬剤の大まかな歴史に関する展示がありました。研修生が日々の診療で使用している薬剤も含まれていることが印象的でした。

3.3

国立がん研究センター（NCC）

まず、国立がん研究センター中央病院 1 階の玄関から 5 階の先端医療科へ向かいながら、外来診察エリアや外来化学療法エリアを含む各フロアの概要について紹介を受けました。患者さんの動線を考慮した各部門の配置について学ぶことができました。
次に、国立がん研究センター中央病院の概要と国内のがん治療・研究において果たされている役割、先端医療科の役割と組織や設備、実際の試験・それに伴う診療の様子、がんゲノムに関するプロジェ
クトなどの紹介がありました。
その後、医師主導国際共同治験プロジェクトの具体例について紹介がありました。国際共同治験において、規制要件や言語、文化的背景の異なる国々と協力しながら、また製薬会社より資金や治験薬の提供を受けながら医師主導で治験を実施していく際の課題やその解決方法、過程について紹介されました。
最後に、先端医療科の病棟を見学しました。第Ⅰ相試験を適切に、また患者さんの安全を確保しながら実施するために様々な点を考慮して設計された設備と、物品の配置等を含め、細やかな配慮がされている様子を知ることができました。

3.4

図 20: 国立がん研究センター前にて

聖路加国際大学

本大学では、公衆衛生大学院の先生方に、日本の大学卒後教育システムについて説明を受け、研修生の出身国のシステムと比較しながらディスカッションを実施しました。特に、各国の医療上の課題を解決するにあたり欠かすことのできない公衆衛生学に関する教育体制について情報交換することができました。各国とも、医学部の教育の段階では非常に基本的な部分のみを学習し、公衆衛生学として学ぶには卒後、新たに大学院等に進学する必要があることがわかりました。聖路加国際大学の公衆衛生大学院では、全授業を英語で実施し、世界各国より教図 21: 聖路加国際病院前にてComprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201917

授や講師を招聘し、日本に限らず各国から生徒を迎えているとのことでした。e-learning システム等を取り入れることで、働きながら学べる環境も整えられており、研修生にとって、日本での卒後教育について考慮するよい機会となりました。
最後に、聖路加国際病院の外来エリアにて、外国人向けの多言語による相談窓口や、礼拝堂など、歴史ある建物を大切に保存・使用しながら、新しい設備も兼ね備えた施設の様子を見学しました。

図 22: 聖路加国際病院前にて

図 23: 聖路加国際大学公衆衛生大学院の先生方と

3.5

東京女子医科大学・早稲田大学連携先端生命医科学研究教育施設 (TWIns)

2008 年 4 月、東京女子医科大学と早稲田大学は東京女子医科大学・早稲田大学連携先端生命医科学研究教育施設(TWIns) を立ち上げました。TWIns の T は東京女子医科大学、W は早稲田大学を意味しています。
当施設への訪問で特に研修生の印象に強く残ったのが、細胞シート技術による立体心筋組織の紹介と、スマート治
療 室 (Smart Cyber Operating Theater; SCOT) へ の 訪
問・デモンストレーションの見学でした。
立体心筋組織は細胞シートを重ねて作成された、血管網を有する厚い組織です。この組織が in-vitro と in-vivoでの試験を経て、動物モデルへ移植し、心機能の改善が確認されていることが紹介されました。
以下は立体心筋組織に関して発表された論文へのリンクです。
https://www.ncbi.nlm.nih.gov/pubmed/25980939
SCOT の見学においては、手術の安全性と正確性を

図 24: SCOT（Smart Cyber Operating Theater）スマート治療室向上するため、様々な医療機器をネットワーク化し、データを一元的に管理・参照し、直感的に各機器を操作する様子をデモンストレーション・体験しました。
外科医の意思決定を支援するための手術部位の 3D 画像の撮影機器や、手術支援ロボットとの連携が可能であることも紹介されました。

図 25: TWIns 前にて

18

4.

4.

結語 ■

結語

5 カ国より 10 名が参加した本研修は、規制当局による MRCT データの評価の視点、日本における臨床現場や臨床試験の現場、教育研究機関や製薬企業における革新的な研究の事例、また日本の教育システムについて学ぶ機会となりました。
本研修の特徴は日本での MRCT の実際を理解し、各国の状況と比較することができる点です。研修生は各国規制の違いについて理解を深め、協力国間における規制調和の重要性を学ぶことができました。日本において薬剤開発の技術やプロセスの革新がどのように進んでいるかを知ることもできました。加えて、研修生同士、また講師の先生方と自身の経験について共有することができました。
研修生からは、本研修は、臨床試験や技術革新における各国と日本の状況を比較するよい機会となったという意見が聞かれました。終了後のアンケートでは、プログラムの内容と DIT スタッフの対応にについて、全体として満足であったという結果が得られています。
一方で、研修期間が限られていたため、DIT スタッフ等とのより具体的なディスカッションや治験に関するケース
スタディの時間が十分に取れなかった点が、改善を希望する点として挙げられており、DIT の研修プログラムにおける今後の課題となりました。

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201919

今後に向けて2019 年 1 月に開催しました「A program focused on comprehensive and collaborative training on medical innovations
adapted to challenges of clinical trials in Asian and African countries」は、5 カ国 10 名の研修生を招聘し 10 日間のプ
ログラムにて実施しました。
研修生からは、聴講した PMDA による規制調和の講義、他国の状況を知りえる機会が提供できたことなどに高い評価を得た一方、ケースを用いたディスカッションなど双方でのよりアクティブな研修の要望がありました。
2019 年度以降は、こうした今回の実践からの学びを踏まえて、連携国を活動の中心に置いて 10 年間の予定で国際共同臨床研究のプロフェッショナルを育成するプログラムをあらたに企画開発、実施して参ります。実施の意図は本報告の冒頭でお示しした通り、国際医療協力に加えて国際共同臨床研究を通じた新規医療技術の開発を行い今なお新興・再興感
染症、希少疾患、難治性疾患などの疾病に苦しむ患者の方々により良い医療を届けるためでありまして、連携国の状況やニーズに合わせたプログラムの提供を模索してまいりたいと存じます。
企画段階に当たっては、先行研究として米国、欧州、アジアにてすでに展開されているプログラムやカリキュラムをイ
ンターネット調査や訪問調査を行い分析し、プログラム設計の基礎材料といたします。調査分析を踏まえてプログラム
コンテンツを定義、2020 年以降、新たに研修生を公募しプログラムを実践して参ります。プログラム実施に当たっては、
オンサイトのプログラム提供のみならず、e-learning やテレカンファレンスなどの手法も織り交ぜながら、より実践的な
国際共同臨床研究をリードするために必要な技術、知識、姿勢を掘り下げるコンテンツを実施していく所存です。企画から実施、評価、改善のいわゆる Plan-Do-Check-Act（PDCA）の 1 サイクルを 5 年としまして、合計 2 サイクル行う計画
としています。
引き続き皆様からのご指導ご鞭撻のほど何卒よろしくお願いいたします。

								国立国際医療研究センター											臨床研究センター								インターナショナルトライアル部								エグゼクティブマネジメント室長

											

20

飯山

達雄

Comprehensive and collaborative training
on medical innovations
adapted to challenges of clinical trials
in Asian and African countries
ENGLISH / 英語Table of Contents

Table of Contents .............................................................................................................................................................. 22
Preface ................................................................................................................................................................................ 23
Acknowledgements ......................................................................................................................................................... 24
List of Acronyms ............................................................................................................................................................... 25
List of Figures and Tables ............................................................................................................................................. 26
1.

2.

3.

Introduction ................................................................................................................................................................ 27
1.1 Description of the Training Program ....................................................................................... 27
1.2 Program Objectives ................................................................................................................... 27
1.3 Participants ................................................................................................................................ 27

Activities at NCGM ...................................................................................................................................................
2.1
		
		
2.2
2.3
2.4
2.5
2.6

Center for Clinical Sciences Department of International Trials (DIT) ........................... 29
2.1.1 Overview of DIT ....................................................................................................... 29
2.1.2 Towards Establishment of an MRCT Network – The DIT Training Plan ....... 30
Bureau of International Health Cooperation (BIHC) ........................................................... 31
Cell Processing Center (CPC) .................................................................................................. 31
Center for Clinical Sciences (CCS) ......................................................................................... 32
Disease Control and Prevention Center (DCC) .................................................................... 32
Biobank ....................................................................................................................................... 33

Activities outside of NCGM ..................................................................................................................................... 35
3.1
3.2
3.3
3.4
3.5

4.

29

Pharmaceuticals and Medical Devices Agency (PMDA) ....................................................
Daiichi Sankyo Company, Limited ..........................................................................................
National Cancer Center Japan (NCC) ....................................................................................
St. Luke's International University ..........................................................................................
Tokyo Women’s Medical University – Waseda University

35
37
37
37

Joint Institution for Advanced Biomedical Sciences (TWIns) ................................................... 38

Conclusion ..................................................................................................................................................................

39

Future Prospects .............................................................................................................................................................. 40
Appendix ............................................................................................................................................................................. 41
Appendix 1
Appendix 2
Appendix 3
Appendix 4
Appendix 5			Training Program Banner .................................................................................... 42
Program Schedule ................................................................................................ 43
Open Seminar Flyer (Japanese) ......................................................................... 44
Open Seminar Flyer (English) ............................................................................. 45
Presentation Handouts ........................................................................................ 46
1. Clinical Trials in DR Congo: Current Situation and Challenges ......... 46

			

2. Clinical Trials: Current Situation and Challenges in the Philippines .. 49

				
				

			

Anggi Gayatri / Nina Mariana

5. Clinical Trials: Current Situation and Challenges in Thailand ............ 65

				

22

Nguyen Chinh Dai / Ngo Thi Phuong Nhung

4. Clinical Trials on Public Institutions in Indonesia .................................. 60

				

			

Angeline Monica Adalin Arcenas / Mylene Urtula Cornel

3. Clinical Trials in Viet Nam: Current Situation and Challenges ........... 54

				

			

Yves Lula Ntamba / Joelle Lumaya Ambis

Borimas Hanboonkunupakarn / Boonjing Siripaitoon

Preface

The situation surrounding the development of new drugs, medical devices, and medical technologies
has significantly changed in recent years. In Japan, there is a need for a system that enables multi-regional
clinical research as continuous effort to ensure quality, increase efficiency, and promote harmonization in drug
development.
In order to develop a reliable network for multi-regional clinical researches, the Center for Clinical Sciences/ Department of International Trials (CCS/DIT) of the National Center for Global Health and Medicine (NCGM)
organized a program for capacity building of health professionals intended to implement multi-regional clinicalresearches in accordance with internationally standardized procedures.
Participants from five countries, from which we currently have representatives in the Department, including
the Democratic Republic of the Congo, Indonesia, the Philippines, Thailand, and Vietnam, were invited to join the
program. This program focused on a comprehensive and collaborative training on medical innovations adapted tothe challenges of clinical trials in Asian and African countries.
Started in 2016, this is the report for FY 2018 of the capacity building division of the CCS-DIT which has a
mission to contribute to the improvement of medical care around the world by developing new methods for theprevention, diagnosis, and treatment of emerging and re-emerging infectious diseases, intractable diseases, rarediseases, and non-communicable diseases through multi-regional clinical research.
From lectures to guided visits at the regulatory authority (Pharmaceuticals and Medical Devices Agency(PMDA)), private industry (Daiichi Sankyo Company, Limited), academia (Tokyo Women’s Medical University– Waseda University Joint Institution for Advanced Biomedical Sciences (TWIns), and St. Luke's International
University), and clinical setting (National Cancer Center Japan (NCC) and NCGM), the 10-day training program forthe 10 participants (2 per country) was a great opportunity to exchange views and knowledge between organizers
and participants and among the participants themselves.
The open seminar which brought together representatives from academia, clinicians, pharmaceutical companies,
and CROs was a good occasion to share about the current clinical trial situation and challenges in each country.
We sincerely thank each one who contributed to the realization of this activity and hope that this program will
be a continuous sustainable system for cooperation with counterpart countries.

							

Hiroshi Watanabe							

Director, Center for Clinical Sciences,							

National Center for Global Health and Medicine														March 20, 2019

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201923

Acknowledgments

There are countless issues to overcome when conducting multi-regional clinical research, including regulatory
harmonization among countries, cooperation with the private sector, and differences in culture and medical
systems. Founded in 2016, the Center for Clinical Sciences-Department of International Trials of the National
Center for Global Health and Medicine aims to promote multi-regional clinical research and contribute to theimprovement of global health by collaborating with counterpart countries. The success of a multi-regional clinicalresearch results from the full commitment of skilled professionals. Thus, training researchers is the key to quality
clinical research.
A 10-day training was held in order to provide some guidance to health professionals from five countries: theDemocratic Republic of the Congo, Indonesia, the Philippines, Thailand, and Vietnam. The guidance is intended tohelp them conduct multi-regional clinical research, with the ambitious goal of providing new medical treatment topatients with emerging and re-emerging infectious diseases, rare diseases, and intractable diseases around the world.
This training could not be executed without the support and guidance from our collaborators in Japan and incounterpart countries. We gratefully thank the PMDA for the lectures provided to participants. Our gratitude also
goes to all the organizations which kindly provided visits and lectures in their facilities, as follows:•

Daiichi Sankyo Company, Limited•

National Cancer Center Japan•

Graduate School of Public Health, St. Luke's International University•

Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University – Waseda
University Joint Institution for Advanced Biomedical Sciences (TWIns)

To all National Center for Global Health and Medicine (NCGM) departments whose staff provided visits andlectures to participants, namely: the Bureau of International Health Cooperation, Cell Processing Center, Clinical
Trial Management Section, Pharmaceutical Division, Disease Control and Prevention Center, and Biobank, we
sincerely acknowledge your cooperation.
We cannot close this chapter without expressing our deep gratitude to all institutions from our counterpart
countries who accepted to send their professionals for this program, including:•

The Democratic Republic of the Congo: University of Kinshasa,
Institut National de Recherche Biomédicale

24•

Indonesia: University of Indonesia, Sulianti Saroso Infectious Diseases Hospital•

The Philippines: University of the Philippines, St. Luke's Medical Center•

Thailand: Mahidol University, Prince of Songkla University•

Vietnam: Cho Ray Hospital, Bach Mai Hospital							

Tatsuo Iiyama																																			

Senior Manager,
Executive Management Office,Department of International Trials
Center for Clinical Sciences,
National Center for Global Health and Medicine							March 20, 2019

List of Acronyms

AMEDJapan Agency for Medical Research and Development

AMR

Antimicrobial resistanceAPEC-RHSC

Asia-Pacific Economic Cooperation Regulatory Harmonization Steering Committee

ATC

Asia Training Center

BIHC

Bureau of International Health Cooperation

CCS

Center for Clinical Sciences

CPC

Cell Processing Center

CRC

Clinical Research Coordinator

CRO

Contract Research Organization

DB

Database

DCC

Disease Control and Prevention Center

DIT

Department of International Trials

FY

Fiscal Year

GCP

Good Clinical Practice

ICH

The International Conference on Harmonisation of Technical Requirements for Registrationof Pharmaceuticals for Human Use

IEC

Independent Ethics Committee

INRB

Institut National de Recherche Biomédicale

IRB

Institutional Review Board

MEXT

Ministry of Education, Culture, Sports, Science and Technology

MHLW

Ministry of Health, Labour and Welfare

MRCT

Multi-Regional Clinical Trial

MRI

Magnetic Resonance Imaging

NCBN

National Center Biobank Network

NCC

National Cancer Center JapanNCGM

National Center for Global Health and Medicine

PDCA

Plan-Do-Check-Act cycle

PMDA

Pharmaceuticals and Medical Devices Agency(R)EID(Re)-Emerging infectious disease

SCOT

Smart Cyber Operating Theater

SOP

Standard operating procedure

TWIns

Tokyo Women’s Medical University-Waseda University Joint Institution for Advanced
Biomedical Sciences

WG

Working Group

WHO

World Health Organization
Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201925

List of Figures and Tables

Number

Title

Fig.1

DIT presentation

29

Fig.2

Function of DIT

29

Fig.3

Example of some training program for clinical research professionals

30

Fig.4

Example of candidate program contents

30

Fig.5

With DIT representatives

31

Fig.6

BIHC presentation

31

Fig.7

In CPC with doctors and other staff

31

Fig.8

CCS presentation

32

Fig.9

Clinical trial medical examination room

32

Fig.10Source data verification room

32

Fig.11

CCS presentation

32

Fig.12

Quarantine wheel chair for patients with infectious diseases

33

Fig.13

Delivery bed in quarantine room

33

Fig.14Presentation by DCC

33

Fig.15NCBN organization structure33

Fig.16

Freezers for sample storage in biobank

34

Fig.17In the biobank facility with the biobank staff

34

Fig.18At the PMDA office35

Fig.19In front of Daiichi Sankyo Company, Limited

37

Fig.20In front of National Cancer Center Japan (NCC)

37

Fig.21

In front of St. Luke’s International Hospital

37

Fig.22

In front of St. Luke’s International Hospital

38

Fig.23

With St. Luke’s International University professors

38

Fig.24The Smart Cyber Operating Theater (SCOT) room38

Fig.25

In front of TWIns

38

Number26

Page No.

Title

Page no.

Table １

Participants and their country

28

Table ２

PMDA-ATC MRCT Seminar program

36

1.

1.

1.1

Introduction ■Introduction

Description of the Training Program

The 2019 NCGM/CCS country-specific MRCT capacity building: "A program focused on comprehensive
and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and Africancountries" was a 10-day training program which aimed to improve capacity of clinical research professionals fromfive counterpart countries in the conduct of multiregional clinical research.
To build a collaborative standardized network for clinical research implementation between Japan andcounterpart countries in Asia and Africa, 10 participants, two per country from the Democratic Republic of theCongo, Indonesia, the Philippines, Thailand, and Vietnam were invited to participate in the program. The program
included lectures, discussions, and visits to the PMDA, a pharmaceutical company, clinical research facilities, andeducational institutions.
Participants attended the Multi-Regional Clinical Trials (MRCT) Seminar 2019 organized by the PMDA Asia
Training Center for Pharmaceuticals and Medical Devices Regulatory Affairs (PMDA-ATC) and gained insight into
the harmonization of regulatory review of MRCT data.
In order to know the current status of research and medical innovations, lectures and visits were provided
from the clinical setting (NCGM, NCC), academia (TWIns and St. Luke’s University), and from a private company(Daiichi Sankyo Company, Limited).
In addition, an open seminar during which participants shared presentations on the state of clinical trials intheir own countries was held.

1.2

Program Objectives

The program aims:•

To discuss about regulations, implementation mechanisms, and issues concerning multi-regional trials
for medical innovations,•

To train professionals who will contribute to the development of clinical trial systems in their countries,
and•To promote cooperation between the National Center for Global Health and Medicine (NCGM) andcounterpart institutions.

1.3

Participants

Medical doctors from 10 institutions in four Asian and one African country who had been involved in clinicalresearch participated in the program.
Following in Table 1 are the participants and their countries.

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201927

Table 1. Participants and their country
Country
The Democratic Republicof the Congo
Indonesia

The Philippines

Thailand

Vietnam28

Institution

Participant Name

University of Kinshasa

Yves Lula Ntamba

Institut National de Recherche Biomédicale

Joelle Lumaya Ambis

University of Indonesia

Anggi Gayatri

Sulianti Saroso Infectious Diseases Hospital

Nina Mariana

University of the Philippines

Angeline Monica Adalin Arcenas

St Luke's Medical Center

Mylene Urtula Cornel

Mahidol University

Borimas Hanboonkunupakarn

Prince of Songkla University

Boonjing Siripaitoon

Cho Ray Hospital

Nguyen Chinh Dai

Bach Mai Hospital

Ngo Thi Phuong Nhung

2.

2.

Activities at NCGM ■Activities at NCGM

2.1

Center for Clinical Sciences Department of International Trials (DIT)

2.1.1

Overview of the DIT

The DIT's project to build a collaborative platform for multiregional clinical trials was extensively explained to participantsby the DIT representatives. It was explained that DIT promotes
information exchange and cooperation among government
agencies, companies, and academic institutions by, for example,
organizing international forums on infectious diseases, while
supporting the seamless execution of multi-regional clinical trials
in emerging countries in compliance with international standards
and country-specific regulations.
In order to develop a better and solid environment for

Fig. 1 : DIT presentation

multi-regional clinical trial programs, DIT is continuously
organizing training programs for capacity building of clinical trial
professionals in Asian and African countries.

International coordinating organization for global clinical research
Concept

Capitalizing on the long history and expertise of NCGM in international medical cooperation, we established an
Academic CRO focusing on global health issues, starting with Emerging and Re-emerging Infectious Diseases. The
Department of International Trials network facilitates medical innovation through Multi-Regional Clinical Trials(MRCTs) with counterparts.
Counterpart countries:
Thailand
VietnamPhilippines Indonesia
DR Congo and others
Activities

 Formulate a platform consisting of human resources from network nations to copewith MRCTs (housed at NCGM)
 Establish clinical trial networking, standardized operational procedures, andmutual cooperation with clinical sites in Asia and Africa
 Implement MRCTs in concurrence with priority of WHO/ nations/ sites

NCGM
clinical research center
Inhouse Collaboration in NCGM

International Harmonization
PMDA-ATC*APEC-RHSC**

Benefits

Partnership with
Industries
Consortium

Health & Medical Strategy• Clinical Innovation Network• Contribute to control of (R)EID,
intractable and rare disease• Medical Innovation supported by larger numbers of cases for (R)EID, intractable
and rare diseases• Reinforcement of new drug/medical device development through MRCTs• Contribution to drug-lag minimization and therapeutic optimization in Asian nations• Improvement of health care and medicines in the world
National Center for Global Health and Medicine

Fig. 2 : Function of DIT

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201929

2.1.2

Towards Establishment of an MRCT Network – The DIT Training Plan

DIT’s training division provided an overview of types of clinical studies and the necessity of clinical trials. They also
insisted on the importance of a continuous updating of knowledge, an increasingly active effort to standardize regulations
and data collection methods for MRCTs in recent years. In addition, they presented the outline of a future training program
to produce global clinical trial specialists.
To develop the program, the DIT analyzed various programs from other organizations involved in clinical trial training, inorder to fulfill the requirements for trained clinical trial professionals.
Trainees will be able to conduct clinical trials in compliance with international standards such as the guidelines issued by
the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human
Use (ICH).
After presentations, the interactive discussion focused on the participants’ opinions about the current program andsuggestions for its improvement, on the state of clinical trials at each home institution, and on their expectations for the
future training program.

For Organized program…
We are developing ourtraining program referring
various global standards
and collaborative activities.

© 2018 National Center for Global Health and Medicine

2

Fig. 3 : Example of some training program for clinical research professionals
https://mrctcenter.org/clinical-trial-competency/
https://www.diaglobal.org/en
https://acrpnet.org/
https://www.who.int/tdr/publications/year/2016/competency-framework-clinical-res/en/
https://www.transceleratebiopharmainc.com/

Candidate contents
Preparation/Principle

Conduct/Procedure

Quality of Trial Data

• Relevant guidelines:
Declaration of Helsinki• Drug development• General considerations forClinical Trials (ICH-E8)• General principles onplanning/designing MultiRegional Clinical Trial (ICHE17)• IRB/IEC• Patient safety andindemnification• Conflict Of Interest (COI)Management• Local Regulations (having
impact for MRCTs)• ICH GCP (E6)• SOP
• Protocol• Investigational ProductManagement• Informed consent• Compliance and issue
reporting• Risk mitigation• Data Entry(Electronic Data
Capture)• Expedited Safety Reporting:
ICH-E2A• Essential documents
Retention (electronic Trial
Master File)• Statistical Principles forClinical Trials(ICH-E9)• Statistical Considerations• Statistical Analysis Plan(SAP)• Data management• Medical Dictionary forRegulatory Activities(MedDRA)• Quality assurance• Risk management Plan
• Monitoring• Sponsor Audit• Regulatory Authority
Inspection• Common TechnicalDocument(CTD)

In addition, Several theme (Performance test for medical device, Specific Regulation in
Japan, Cutting-age Medical Technologies etc…) can be optional materials.
© 2018 National Center for Global Health and Medicine

Fig. 4 : Example of candidate program contents

30

1

2.

Activities at NCGM ■Fig. 5 : With DIT representatives

2.2

Bureau of International Health Cooperation (BIHC)

As presented by the BIHC representative, theNCGM through the BIHC has a 40-year history
of international cooperation, conducting a wide
range of technical cooperation projects and policy
proposals. The BIHC's technical cooperation projects
involve public health, maternal and child health,family planning, infectious diseases control, and thedevelopment of medical facilities.
In a project to build a medical facility, for example,
the BIHC is providing comprehensive support for
opening, managing, and maintaining the facility,

Fig. 6 : BIHC presentation

which includes support for medical technology
transfer, installation of medical systems and emergency care systems, hospital management (e.g., financial
management and equipment management), and human resource development (e.g., education of nurses andother medical professionals).
One of the BIHC's strengths is its ability to provide policy-related advice and proposals that reflect local
circumstances and based on lessons learned and knowledge acquired through previous technical cooperation projects.

2.3

Cell Processing Center (CPC)

Cell therapy has become an innovative treatment for
many degenerative and non-communicable diseases.
To get good quality cells to be used in the therapeuticareas, cells should be treated and cultured under somespecific requirements.
The CPC is a series of strictly particle -and microbialcontrolled clean rooms equipped with clean benches andisolators to prevent microbial contamination and ensure

Fig. 7 : In CPC with doctors and other staff

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201931

cell culture.
The CPC was introduced to participants by two head researchers. One focus is the pancreatic islet transplantation
procedure which consists of pancreatic cell culture followed by successful transplantation to Diabetic type 1 patients withuncontrolled glycemia despite insulin therapy and patients with pancreatitis. The presented study provides hope to better
improvement of the diabetic’s quality of life and in the overall impact to society.

2.4

Center for Clinical Sciences (CCS)

After a brief introduction about the organization of
the CCS and its clinical trials-related activities, detailed
explanations on the informed consent process were given
to participants. Emphasis was on the role taken by theclinician and the Clinical Research Coordinator (CRC)
from pre-screening to recruitment of patients.
Participants then visited the Clinical Trial Management
Section and the access-restricted temperature-controlledstorage room located in the Pharmaceutical Section.
During their visit, participants could see the trial-related

Fig. 8 : CCS presentation

documents storage and private monitoring rooms.
Discussion focused on how: to protect patient privacy,
to keep the trials related document secure, to use
smartphones for the remote control of the storage
temperature, and to manage equipment in order to ensure
consistent data collection.

Fig. 9 : Clinical trial medical examination room

Fig. 10 : Source data verification room

2.5

Fig. 11 : CCS presentation

Disease Control and Prevention Center (DCC)

Activities at the DCC were divided into two parts: the lecture and the facility visit.
During the lecture, DCC’s activities were presented. The DCC is engaged in the development of medical experts andinfectious disease specialists involved in the prevention, diagnosis, and treatment to fight against antimicrobial resistance

32

2.

Activities at NCGM ■as well as infections.
Aside from clinical care, the DCC has a network with otherinstitutions in and out of Japan for collaboration in infection
control, education and training. The DCC is also engaged inrisk assessment and actions to protect borders by developing
researchers who detect infections early while assessing the needfor rapid response.
During the visit, participants could observe some medical
wards of the DCC, such as the well-equipped quarantine roomwith a movement-controlled system to prevent any contaminationor spread of emerging and re-emerging infectious diseases while
keeping the patient comfortable and the staff free to administercare safely.

Fig. 13 : Delivery bed in quarantine room

2.6

Fig. 12 : Quarantine wheel chair for patients with
infectious diseases

Fig. 14 : Presentation by DCC

Biobank

While visiting the Biobank facilities, the staff in charge presented the organization of the National Center Biobank
Network (NCBN). The Biobank is part of the NCBN which is a network of six biobanks located at the six national medical
centers in Japan. The six national biobanks store samples related to their respective specialties.

Fig. 15 : NCBN organization structure

https://ncbiobank.org/organization/index.php

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201933

While each national center biobank collects its related
sample, there has been developed a common platform
for the management. The application process for getting
access to the biodata and the research support services
are provided by the central biobank secretariat.
Any researcher who wishes to use biodata can apply tothe secretariat and the acquisition of samples is possible
for anyone who fulfills the requirements.
The NCGM biobank stores samples (blood, sputum,etc.) obtained from patients with infectious diseases,
metabolic disorders, and immune-related disorders. The

Fig. 16 : Freezers for sample storage in biobank

facility has a remote temperature-controlled room whichcontains numerous freezers adapted for the storage.
It is worth noting that all sample collection ispreceded by a strict informed consent process and data
are shared anonymously to protect patient privacy.
NCGM biobank : ncgmbb@hosp.ncgm.go.jp

Fig. 17 : In the biobank facility with the biobank staff

34

3.

3.

3.1

Activities outside of NCGM ■Activities outside of NCGM

Pharmaceuticals and Medical Devices Agency (PMDA)

There is a strong collaboration between the PMDA and the NCGM in terms of diverse activities.
Participants joined the Multi-Regional Clinical Trials Seminar 2019 organized by the PMDA Asia Training
Center (PMDA-ATC) for Pharmaceuticals and Medical Devices Regulatory Affairs .
This seminar is held annually for representatives of relevant regulatory authorities in various countries. Its
objective is to promote regulatory harmonization concerning drug development based on the Japanese experiencein the reviewing process for drugs and medical devices. This process follows necessary requirements forplanning, designing and implementation of clinical trials, clinical data assessment, and post-marketing benefitrisk assessment, all in accordance with the ICH guidelines. Lecturers therefore presented concrete examplesof these, with further focus on review toward approval including GCP inspections. Lectures were provided byexperts from diverse specialties including PMDA, academia, and industry.
In addition to lectures provided by the organizers, representatives of regulatory authorities from each country
presented an outline of the approval review systems and procedures in their countries and discussed issues
involving the implementation of the ICH E17 Guideline.
This was a good opportunity for participants to be familiar with the drug review and approval processes ofcounterpart countries and to get a wide view from different stakeholders, including academia, regulatory
authorities, and pharmaceutical companies.
■ Web page on the PMDA-ATC MRCT Seminar: https://www.pmda.go.jp/english/symposia/0138.html

Fig. 18 : At the PMDA officeComprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201935

Table ２: PMDA-ATC MRCT Seminar program(The following information comes from the PMDA web page and lists only the sessions attended by the participants.)

PMDA-ATC Multi-Regional Clinical Trial (MRCT) Seminar 2019
Offered by Asia Training Center for Pharmaceuticals and Medical Devices Regulatory Affairs
DATE: January 21-24, 2019 / VENUE: PMDA
DAY 1 (January 21, 2019)
Key note speech
Strategies and challenges for drug development- Future movements and backgrounds of development strategies History of drug evaluation using overseas data in Japan Q&A
Scientific insights about ethnic factors Q&A<Session 1>
Introduction of review systems and regulations by participants<Session 2>
International cooperation and alignment•
Global platform for medical innovation as an Academic Research Organization (ARO)
Challenge for global cooperation of regulatory agencies•
Q&A
DAY 2 (January 22, 2019)<Session 3>
Points to consider when planning and designing MRCT
Points of attention for consultation about MRCT from PMDA’s experience•
Case study -Planning and designing MRCT•
Q&A<Session 4>
Points to consider when evaluating results
Statistical considerations for MRCT based on the ICH E17 guideline•
PMDA’s experiences to review MRCT results•
Q&A
DAY 3 (January 23, 2019)<Session 5>
Considerations for MRCT operations
Practical issues and solutions on MRCT operations (Investigator’s viewpoint)••
Practical issues and solutions on MRCT operations (Industry’s viewpoint)
Q&A
DAY 4 (January 24, 2019)<Session 6>
Regulatory review based on results of GCP inspection
How to perform GCP inspection in Japan -Role of GCP inspection in review process••How to take GCP inspection results into consideration for review from reviewer’s perspective•
Applicant’s experiences to undergo GCP inspection
Trial site’s experiences to undergo GCP inspection•
Q&A<Session 7>
Post-market safety evaluation of approved drugs based on MRCT
Global standards for pharmacovigilance•
Risk management plan based on the multi-regional clinical development -from perspectives of pharmaceutical•companiesRisk management based on the multi-regional clinical development - from perspectives of regulatory agencies •
Q&A

36

3.

3.2

Activities outside of NCGM ■Daiichi Sankyo Company, Limited

Research and drug development has been the focus of theDaiichi Sankyo Company, Limited for more than one decade.
This global company has successfully launched products thathave enhanced many lives around the world.
Activities at the facility were highlighted by a lectureduring which the company representative gave a detailed
explanation of the drug discovery process, from laboratory toclinical trials including animal studies. Noteworthy is that thisprocess is very long and costly.
Following the lectures, participants were guided to visit a

Fig. 19 : In front of Daiichi Sankyo Company, Limited

series of well-equipped laboratories which use cutting-edge technologies for the drug discovery process.
Many of the agents such as antibacterials produced from this company are used by all the participants in their daily
practice.

3.3

National Cancer Center Japan (NCC)

After a brief explanation about the hospital structure andservices, the researcher from the Department of Experimental
Therapeutics presented the current situation of clinical trials in
the National Cancer Center Hospital and the achievements whichhave been made in terms of drug development.
Concerning clinical trial-related activities, the National
Cancer Center Hospital has been involved in national trials andnow participating in international clinical trials.
In MRCTs, the National Cancer Center Hospital has been facing
many challenges such as the cultural and language differences,varying regulatory requirements and management of funds andtrial drugs received from pharmaceutical companies.
National Cancer Center Hospital’s researchers are also
conducting trials for cancer genomics.
Participants much appreciated viewing the well-equippedfacilities of the Phase 1 unit for clinical trials.

3.4

St. Luke's International University

Fig. 20 : In front of National Cancer Center Japan(NCC)

To be familiar with the education system in Japan,
participants visited St. Luke's International University.
The Dean of the Graduate School of Public Health presented
the organization of the program which is mainly designed for
current working professionals.
The share time was mainly focused in the comparison
between the Japanese education system and that of eachparticipant country.
All courses are provided in English either onsite or using the

Fig. 21 : In front of St. Luke’s International Hospital

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201937

e-learning system by teachers from multiple borders.
After the exchange, participants were able to visit the multilingual consultation desk, which is a rare service forforeign patients in Japan.

Fig. 22 : In front of St. Luke’s International Hospital

3.5

Fig. 23 : With St. Luke’s International University professors

Tokyo Women’s Medical University – Waseda University
Joint Institution for Advanced Biomedical Sciences (TWIns)

In April 2008, under the direction of the Tokyo Women’s Medical University and the Waseda University, the Tokyo
Women’s Medical University - Waseda University Joint Institution for Advanced Biomedical Sciences (TWIns) was
created. TWIns is a research and education center for medical engineering. The term “TWIns” stands for the “T” inTokyo Women’s Medical University and the “W” in Waseda University.
Two strong points dominated the visit at the TWIns, first the presentation about the three-dimensional cardiac
tissue fabricated using the cell sheet technology and the demonstration of the Smart Cyber Operating Theater (SCOT).
The 3-D cardiac tissue is a thick vascularized tissue created by layering three cell sheets for good vascularization.
The tissue has been used successfully both in vitro
and in vivo . In vivo , cardiac transplantation in someanimal models improved their heart function. This
innovation intends to be the future hope for thetreatment of heart failure and other cardiopathies.
Following is the link of the published paper related tothe 3-D cardiac sheet.
https://www.ncbi.nlm.nih.gov/pubmed/25980939
The SCOT is a cutting-edge operating room thatuses computing and networking technologies for the
improvement of safety and precision of surgery, inFig. 24 : The Smart Cyber Operating Theater (SCOT) room

this case especially neurosurgery. This is a decisionmaking navigation system which helps the surgeon
achieve a 3-D image of the lesion during the operation
and with the integration of the robotic device; theSCOT helps for the precision guidance.

Fig. 25 : In front of TWIns

38

4.

4.

Conclusion ■Conclusion

The 2019 NCGM/CCS country-specific MRCT capacity building: “A program focused on comprehensive andcollaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries", a10-days training program which brought together 10 participants from 5 countries was an opportunity to learn about theregulatory view for managing MRCT’s data, to familiarize with the Japanese clinical practice and research, to experience
the innovative researches from academia as well from industry, and to familiarize with the education system in Japan.
The strength of this program was due to the fact that participants could understand the Japanese side of the MRCTand could compare with their local knowledge. Participants could understand how much regulations are various but there
is an important trend of harmonization between collaborative countries. They also could see the advancement of theinnovations in the drug development process and engineering. In addition, they could share their own experience with otherparticipants and with lecturers.
In the view point of participants, the program was a good opportunity for them to see a different clinical trial andinnovation world from their respective countries.
Globally, they were satisfied with the content of the program and with the support of the DIT staff. Nevertheless, they
were concerned about the short timing of the program which didn’t allow them and the DIT staff to have more practical
discussion of clinical trial cases.
This aspect is the weakness of the training program.

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201939

Future Prospects

Ten researchers from five countries were invited to participate in the 10-day training program held in January
2019, which focused on comprehensive and collaborative training on medical innovations adapted to the challenges ofconducting clinical trials in Asian and African countries.
The participants greatly appreciated the lecture on regulatory harmonization given by experts from the PMDA, as
well as the opportunity to learn about situations in various countries.
At the same time, however, they suggested that we should include more active training activities such as discussions
with experts based on case studies.
Starting in FY 2019, based on the lessons learned from the implementation of the previous programs, we will planand develop a new training program to produce professionals specializing in multi-regional clinical trials, which will be
implemented in counterpart countries over a planned period of 10 years.
As discussed at the beginning of this report, the purpose of the program is to provide international cooperationand develop new medical technologies through multi-regional clinical research and to thereby provide new medical
treatment to patients with emerging and re-emerging infectious diseases, rare diseases, intractable diseases, andnon-communicable diseases.
We will explore ways to offer a program that will suit the situations and needs of counterpart countries.
In the planning stage, we will conduct internet-based research and make research visits in order to analyze
programs and curricula that have already been implemented in the United States, Europe, and Asia. The analysis will
provide basic information needed to design the program.
Based on our research and analysis, we will determine the program content and will publicly solicit applications fromprospective participants and begin implementation of the program in 2020. We intend to offer activities that will enable
participants to develop skills, knowledge, and attitudes necessary for leading practical multi-regional clinical trials.
Such activities will include on-site visits, e-learning, and teleconferences. We plan to apply the so-called, Plan-DoCheck-Act (PDCA) cycle to the program implementation, with two cycles lasting 5 years each.
We appreciate the continued guidance and encouragement provided by the relevant organizations andprofessionals.

40							

Tatsuo Iiyama																												

Senior Manager, Executive Management Office,Department of International Trials
Center for Clinical Sciences,
National Center for Global Health and Medicine

別添 / Appendix

別添 1 / Appendix 1

France

研修プログラムポスター / Training Program Banner

NCGM
Thailand

DRCongoVietnam
The Philippines
Indonesia

The 2019 NCGM/CCS country-specific
MRCT capacity building“ A program focused on comprehensive and collaborative training
on medical innovations adapted to challenges of clinical
trials in Asian and African countries."
Tokyo, January 16-25,201942別添 / Appendix ■別添 2 / Appendix 2

スケジュール / Training Program Schedule

The 2019 NCGM/CCS Counry-Specific MRCT Capacity Building
Duration: Jan. 16- Jan.25, 2019
Date

am/pm

【Day1】

AM

Jan. 16, 2019【Day 2】

ArrivalAM

Orientation: Life in Japan, Self introduction
Introducing NCGM
Introducing Department of International Trials (DIT)
NCGM
Introducing Bureau of International Health Cooperation(BIHC)
Introducing Cell Processing Center(CPC)

Jan. 19, 2019

Airport-> NCGM

PM

Visit to Daiichi Sankyo Company, Limited

NCGM ->
Daiichi Sankyo
Company, Limited

AM

Visit to National Cancer Center Japan (NCC)

NCC -> NCGM

【Day 3】【Day 4】

Venue

PMJan. 17, 2019

Jan. 18, 2019

Program

PM

AM

Site tour in NCGM
Introducing Center for Clinical Sciences(CCS)Introducing Disease Control and Prevention Center (DCC)
Introducing Biobank
Visit to National Museum of Emerging Science and Innovation
Miraikan

NCGM

Miraikan

PM

Discussion on Japan's cutting edge medical technology

AM

Visit Open Seminar Session venue

Jan. 20, 2019PM

Discussion and preparations for the Open Sminar Session【Day 6】

AM

Participate in PMDA-ATC MRCT seminar 2019

PM

Participate in PMDA-ATC MRCT seminar 2019

AM

Participate in PMDA-ATC MRCT seminar 2019
Visit to St. Luke's International University Graduate School

PMDA-> St. Luke's
International University

PM

Participate in PMDA-ATC MRCT seminar 2019

St. Luke's International
University -> PMDA

AM

Participate in PMDA-ATC MRCT seminar 2019

PMDA -> TWIns

PM

Visit to Tokyo Women’s Medical University-Waseda University
Joint Institution for Advanced Biomedical Sciences (TWIns)
Open Seminar Session;
Clinical Trials-Current Situation and Challenges(Presentation from each country)

TWIns -> NCGM

AM

Participate in PMDA-ATC MRCT seminar 2019
NCGM DIT Lecture/Discussion;
Towards a MRCT's Network Establishment-The DIT Training Program-

PMDA -> Meeting
Room ->PMDA

PM

Participate in PMDA-ATC MRCT seminar 2019
Closing Ceremony; Program Completion Certificate Ceremony

PMDA ->NCGMAM

Fly back Home

NCGM->Airport【Day 5】Jan. 21, 2019【Day 7】Jan. 22, 2019【Day 8】Jan. 23, 2019【Day 9】Jan. 24, 2019

【Date 10】Jan. 25, 2019

NCGM

PMDA

PM
Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201943

別添 3 / Appendix 3

成果報告会案内（日本語）/ Open Seminar Flyer (Japanese)

D6JCL+G>@H+7L?A<5+=7+:L;

)*"%,1/$'.02

&!/-#



(

����������2045�������������������������������������������
�������������R�������������������R��������������������
����������������������
����������������2��������������������������������������
����������������������������������
�����������������������������������������������o������2���������������������������������������������������������
��������������������R��������
�����������������
EK9IH
����������� oR����������� ��������������������������
����������� ����������������������
����������� ���������������������
����������� �����������������������
����������� �������������������
����������� ��N������������������
�����������������������������������o��R�����������������-.R����������������������
���������������
����������������������
����������������������������
����������������
0������������������������������
44

別添 / Appendix ■別添 4 / Appendix 4

&'$$"成果報告会案内（英語）/ Open Seminar Flyer (English)##!%&

!$%!"!%!!  "!#$%!&%'$$!&&'&"!! !%!("'$"'!&$(!'$( 
���J���� �� ������T�����������T���T���������J���G����������G������G J���G��� ����� ���G� ���� GTJ
�G�G��G �� �T�������������G��GTJ����T�������������T�����G��������������TJ��������������G���������������
��������T���T�����G���G���T�����G���T���������J���G���������G�����T�������������������T��G�����T����GT�������
�G���TG����T������������G����G����GTJ���J���T�����������J��T������G�����T��G�����J�����G�T�������
������T�����������T���T���������J���G������G���J���G�����GTJ�����G������J���G�����������������
�����T��������T��G������T������������T����������������������G���T��������J�G���G�����������������������������G�����T��G�����J�������T�JG�����G�T�T�������G���G��
J�������J����G�T������������T�����������J�����������T�����������������G���GJ���G������G���T������
��������T��GT�G��������T�������G�T����������GTT�J�������������T�������T��������������������T��G��
���G���������T������G���T�GTJ���G���T�����������������������T�����G������G���T�)$"$ )��f)&���f)� ���T�T���f)����f��������T�G���T�����������T�
��f����,f��������T�G���T��������������T���,f����,f)�������T�G���T������������G��,f�����f&�������T�G���T�������TJ�T���G
��f&����f(�������T�G���T��������G��GTJ
��f(����f)& �����T� ���G���

������G���G�������GT��J��G���������f�GT�G���()��(&�����f)&���f)&g���������T��f&&h
��T��f�G���TG����T������������G����G����GTJ���J���T������G�����T����������T����T�����
�T��������f����g�������������G���T��������Jh�������G���T�����f�������G���T�����
�G������GT��f,&�������g�������G���T���T��T�����T�����������T��G��������Jh�GT��G��f�T�����
����f �G���TG����T������������G����G����GTJ���J���T�
��T�G��������f&)�,((.�&�����G����J����T��������T���������

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201945

別添 5 / Appendix 5

各国成果報告会発表資料 / Presentation Handouts

1. Clinical Trials in DR Congo: Current Situation and Challenges
Yves Lula Ntamba / Joelle Lumaya Ambis

Culture••Clinical Trials in DR Congo:
Current situation and Challenges•

More than 400
tribes
Official language(french)
4 national languages(lingala mostwidespread within
the country)

Yves Lula, MD
Joelle Lumaya, MD, MSc

1

4OutlinePublicsector2.
•DRC:
overview

1•DRC:
culture4.
•Healthsystem•Health
problems

3.

•Clinical
trial:
status andinfrastructures,
regulatory
matters,
networks,
examplesHealth system•Most healthcare services charge afee (payment for every single
intervention)•No public insurance•Assistance provided by NGOs &donors to fight high-burden
diseases•Private sector still growing (ineach level), agreements with PHD
to be involved in the national
policy6.
•Challenges
andopportunit
ies

26PHD

516HZ

5.

2

2

5

Health problems

Democratic Republic of Congo (DRC)
•
•
•
•
•
•
•

2nd largest Sub-Saharan Africa country(2,345,409 km2)
Population: > 70 millions (consumers)
Borders: 9 countries and Atlantic Ocean
Human Development Index: 0.457 (176th)
Poor accessibility within the country(flight needed to reach some places from
Kinshasa)
Urban (30%), rural (70%)
Climate (tropical wet), 2 seasons (rainy
and dry)

By Connormah - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8986316

346ü 10 most causes of deaths, all ages

ü Ten most causes of deaths < 5

•
•
•
•
•
•
•
•
•
•

•
•
•
•
•
•
•
•
•
•

Malaria
Lower respiratory infection
Tuberculosis
Diarrheal diseases
Cerebrovascular diseases
Ischemic heart diseases
Protein-energy malnutrition
HIV/AIDS
Preterm birth complications
Birth asphyxia and trauma

Malaria
Lower respiratory infection
Tuberculosis
Diarrheal diseases
Protein-energy malnutrition
Neonatal preterm birth
Neonatal encephalopathy
HIV/AIDS
Neonatal sepsis
Congenital defects

6

｜別添 5 / Apendix 5 ｜ 1.

Health problems: emerging issues

Clinical trials: regulatory matters

Ebola outbreak (As of 15 January: 614 confirmed

Non communicable diseases

Clinical Trials in DR Congo: Current Situation and Challenges ■cases, 407 deaths, 237 people discharged from hospitals)

WHO survey
hypertension
prevalence (2006)27%

Directorate of pharmacy and medicine (DPM,
MoH)
Advertisingcommission

Drug approvalcommission• CTD format (ICH), 5 modules• Harmonization procedures with
SADC countries• Quarterly meeting• Existing guidelines• Guidelines not existing

Pharmacovigilance
commission

Clinical trial
commission• Half yearly meeting• Guidelines drafted• Newly created• Guidelines drafted
10

7

10

Health problems: neglected diseases

Clinical trial: networks•ARCEAU (local)•CANTAM (Central Africa)
DiseaseHookworm
infection
Schistosomiasis
Ascariasis
Trichuriasis
Lymphatic
filariasis
HAT
Leprosis

Estimated cases
31 million

Rank in Africa
2nd

15 million
23 million
26 million
49 million at risk

3rd
3rd
2nd
2nd

10,269–18,592
3,621

1st
1st

üPublic Health School, ClinicalPharmacology, Biamba Marie
Hospital, Swiss Tropical InstituteüGlobal clinical researchütropical diseasesüCameroon, Gabon, Republic ofCongo, DRC (Clinical Pharmacology)
ü10 research institutions anduniversitiesüHIV, TB, Malaria, Neglected tropicaldiseases••Public Health
School & OxfordNorth Carolina
Universities

Rimoin AW, Hotez PJ (2013) NTDs in the Heart of Darkness: The Democratic Republic ofCongo’s Unknown Burden of Neglected Tropical Diseases. PLoS Negl Trop Dis 7(7): e2118.

HDSS/Research
centre Kimpese•Tropical Medicine
Department/Universityof AntwerpüMalaria mainly

•

DNDi

ü Neglected
tropicaldiseasesüMalaria mainly

8

11

Clinical trial: examples (ongoing)

Clinical trials: status and infrastructures
None

INRB(JICA Centre)
None
UNIKIN

Discovery andDevelopment

PreclinicalResearchPhase 1

Universities
Sponsor trials centers

Phase 2Phase 3Phase 4

Study title

Condition

Intervention

Location

SponsorInvestigational Therapeutics for theTreatment of People With Ebola Virus
Disease (multioutbreak, multicentre
RCT)

Ebola

Zmapp, mAb114,
Remdesevir, REGNEB3

Beni (Butembo
upcoming)

NIH (As of 6 Jan, 44
patients enrolled)

Cohort Event Monitoring Study of
Pyramax®

Malaria

Pyramax

DRC (Kinshasa,
Kimpese), Congo,
Gabon, Cameroon,
Ivory Coast,
Switzerland

MMV/Shin Poong

Prospective Study on Efficacy and
Safety of SCYX-7158 in Patients Infectedby Human African Trypanosomiasis Due
to T.b. Gambiense

Human African
Trypanosomiasis

Acoziborole

Many locations (12) in
DR Congo and 1 site in
GuineaDNDi

DIAgnostics for Multidrug Resistant
Tuberculosis in Africa

MDR
Tuberculosis

Diagnostic Tesst:
Deeplex test,
InSilixa chip assay,
GeneXpert
Fluorescein
DiAcetate (FDA)

INRB, ITM Antwerp,
some countries

Laboratoire deRéférence desMycobactéries

59 studies registered in Clinicaltrials.gov
Laboratories
institutions

andresearch• Institut national de recherche
biologique(INRB)• National program for TB control(Mycobacterium lab)

Research institutions (Universities)
University of Kinshasa
University of Lubumbashi
UEA, UCB (Universities of Bukavu)
University of Goma

• Institut de recherche sur lessciences de la santé (IRSS)

Catholic University of Graben• Centre de recherche en médecine
tropicale de l’Ituri

Kongo University

University of Kisangani

Others provincials and privates Universities

There is a lack of facilities and equipment for drug development and clinical trials

9

9

12

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201947

Clinical trial: examples (ongoing)
Study title

Condition

Intervention

Location

Sponsor

Diagnostic Tools for Human African
Trypanosomiasis Elimination and Clinical
Trials: Early Test-of-cure (DiTECT-WP4)

African
Trypanosomia
sisDiagnostic Test:
RNA andneopterin
detection

Many sites in the
country

Institute of Tropical
Medicine (Belgium)

Arresting Vertical Transmission of Hepatitis B
Virus (AVERT-HBV)

Hepatitis B

Tenofovir
Disoproxil
Fumarate,
Monovalent HBVvaccine

Kinshasa

University of North
Carolina

Community Access to Rectal Artesunate for
Malaria (CARAMAL)

Malaria

Rectal artesunate

DR Congo, Nigeria,
UgandaUNITAID, SWISS TPH,
CHAI, UNICEF

Fexinidazole in Human African
Trypanosomiasis Due to T.b. Gambiense at
Any Stage (FEX009)

Human African
Trypanosomia
sisFeninidazole

Many locations in DR
Congo

DNDi

13

Clinical trials: challenges
•
•
•
•
•

Poor infrastructures in rural and remote areas (roads, rivers) →logisticalchallenges
Security concerns in East part of country
Language barriers
Limited number of scientist trained in clinical trial
Lack of adequate facilities/equipment dedicated to clinical trials

14

Clinical trials: opportunities• Variety of diseases (re-emergent, neglected, non-communicable diseases)• Gene diversity of inhabitants (pharmaco-genetics study)• Co-existing of various patterns of certain diseases (malaria patterns“tropical-equatorial-mountain”)• Cost-effectiveness (rapid inclusion “less time”, reduced cost)• Existing local CRO (Swiss TPH, DNDi) and ethics committees• Improvement of regulatory authority over time

15

48

16

｜別添 5 / Apendix 5 ｜ 2.

Clinical Trials: Current Situation and Challenges in the Philippines ■2. Clinical Trials: Current Situation and Challenges in the Philippines
Angeline Monica Adalin Arcenas / Mylene Urtula Cornel

    Clinical Trials: Current Situation
andChallenges in the Philippines
MYLENE U. CORNEL, MD
ANGELINE MONICA A. ARCENAS, MD
PHILIPPINES

1

44© 2018 National Center for Global Health and Medicine

Country Populations in 20 Years(1997-2017)

JAPAN
126.8M
PHILIPPINES
104.9 M
VIETNAM
95.5M
DCR
81.34MTHAILAND
69.04M
MALAYSIA
31.6M

22© 2018 National Center for Global Health and Medicine

5© 2018 National Center for Global Health and Medicine

5

Key Indicators for PH

Philippines• archipelago of 7,500
islands• Capital : Manila• 12th most populous
country• 3 seasons :• hot and dry : March toMay• rainy : June to October• moderate and best to visit: Nov to Feb© 2018 National Center for Global Health and Medicine

33

Poverty headcount ratio at $1.25 a day (PPP) (% of population)(2015)1

21.6✖

Gender inequality index rank (2018)2

8 of 149✔

Human development index rank (2018)3

113 of
189✔

Total expenditure on health as a percentage of GDP (2014) 4

4.71

Private expenditure on health as a percentage of total
expenditure on health (2014) 4

65.72

General government expenditure on health as a percentage of
total expenditure on health (2014)4

10.10© 2018 National Center for Global Health and Medicine

Sources:
1 https://data.worldbank.org/indicator/SI.POV.NAHC?locations=INPH&name_desc=false
2 http://www3.weforum.org/docs/WEF_GGGR_2018.pdf
3 http://hdr.undp.org/en/composite/HDI
4 https://psa.gov.ph/national-health-accounts-press-releases
6
http://apps.who.int/gho/data/node.cco.ki-PHL?lang=en

6Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201949

Research Interest• In clinical trials, Philippines• 3rd in SE countries (US NIH)
• 8th worldwide (European Medicines Agency reports)

Q1: What are the potentials forhandling clinical trials in thePhilippines?

7

Potentials
A. Research interest is high ; willingness toparticipate
B. Government support : Adequate funds for public
and private sectors
C. Skilled and experienced humanresource/professionals
D. Infrastructure and Connectivity
E. Regulatory environment
F. GCP compliance88© 2018 National Center for Global Health and Medicine

Research Interest• High level of interest in research both in private and public hospitals• Investigator-initiated trials• Sponsor-initiated trials• Willingness to participate in clinical trials and research• Encouraged even in postgraduate courses and fellowship programs© 2018 National Center for Global Health and Medicine

50

CTTO

99

• As of April 2018,• 882 clinical trials• 179 ongoing trials in major therapeutic areas• Respiratory disease and Lung disease• Communicable disease and Infectious disease• Diabetic/Metabolic/Endocrine disorders• Immune system disorders• Vascular disease and• Oncology© 2018 National Center for Global Health and Medicine

Source:https://www.sciencedirect.com/science/article/pii/B9780123815378100111
https://epsi-global.com/locations/philippines/article01.html
http://www.pcrp.org.ph/pdf/GuidelinesversionLR.PDF
https://clinicaltrials.gov/ct2/results/browse?cntry=PH&brwse=cond_alpha_all

10
10

Government Support• National Unified Health Research Agenda(2017-2022)•
Guides health research and development
efforts in the country•
Envisioned to be inclusive, realistic, andcollaborative• Documents reviewed:
1.
2.
3.
4.
5.

Philippine Health Agenda 2016-2022
DOH Philippine Medium Term Research Agenda
DOST Harmonized Research Agenda
Philippine Development Plan 2017-2022
Sustainable Development Goals

1111© 2018 National Center for Global Health and Medicine

Adequate funds
Clinical Trials in PH (2017)

Funding Agency

AmountGovernment (51)

PHP 194M or
JPY 405M

Private (44)

PHP 3B or JPY
6B

Private (6)Undisclosed

SOURCE: 2017 Annual Report of Philippine Health Research
Registryhttp://registry.healthresearch.ph/index.phoption=com_phocadownload&view=file&id=14&Itemid=19© 2018 National Center for Global Health and Medicine

1212

｜別添 5 / Apendix 5 ｜ 2.

Human Health Resources

Health Professional

Total

Nurses90 308 8.6

Midwives

43 044 4.1

Doctors

40 775 3.9

Clinical Trials: Current Situation and Challenges in the Philippines ■Infrastructure and Connectivity• Major private hospitals have world-class facilities• JCI-accredited• Major government hospitals have complete diagnostic equipment• ISO accredited• Internet connectivity available

HCW density/
10000 pop

Medical Technologists 13 413 1.3

Source: Dayrit MM, Lagrada LP, Picazo OF, Pons MC, Villaverde MC. The Philippines Health System
Review. Vol. 8 No. 2. New Delhi: World Health Organization, Regional Office for SouthEast Asia; 2018.

13© 2018 National Center for Global Health and Medicine

13© 2018 National Center for Global Health and Medicine

16
16

Infrastructure and Connectivity

Infrastructure and Connectivity• Major private hospitals haveworld-class facilities• JCI-accredited• Major government hospitals
have complete diagnostic
equipment• ISO accredited• Internet connectivity
available• Physical infrastructure of the Philippine health sector• 1,224 hospitals• 2,587 city/rural health units• 20,216 Barangay Health Stations© 2018 National Center for Global Health and Medicine

CTTO

14
14

© 2018 National Center for Global Health and Medicine

17
17

Clinical Trial Regulatory Process

Infrastructure and Connectivity• Main regulatory institution is the Philippine
Health Research Ethics Boards (PHREB)• Level 1 : reviews researches with minimal risk toparticipants• Level 2: reviews all types of researches EXCEPT
clinical trials required for FDA registration of new drugs.
Post marketing studies may also be reviewed.
• Level 3: reviews ALL types of researches including
studies required for FDA registration of food, drugs anddevices• Physical infrastructure of the Philippine health sector iscomposed of:• 1224 hospitals• 2587 city/rural health units• 20 216 BHSs

© 2018 National Center for Global Health and Medicine

1515© 2018 National Center for Global Health and Medicine

1818Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201951

Clinical Trial Regulatory Process

Increasing Number of Diseases• Numerous accredited research
ethics committees - (81)
• Level 3 – 47
• National Capital Region : 28
• Level 2 – 21
• Level 1 – 1319

© 2018 National Center for Global Health and Medicine

19© 2018 National Center for Global Health and Medicine

2222Increasing Number of Diseases

Q2: What are the health challenges in thePhilippines?

20© 2018 National Center for Global Health and Medicine

23
23

Health Challenges• Increasing number of diseases• Infectious• Non-communicable• Accidents/ Mental health• Some laboratories are NOT readily available in the country• Inaccesibility of the health services to rural areas• Expensive medications and treatment• Focused on provision more than research© 2018 National Center for Global Health and Medicine

52

CTTO
21

Q3: What can be done to make collaborations
more efficient in the future?

21

24

｜別添 5 / Apendix 5 ｜ 2.

Clinical Trials: Current Situation and Challenges in the Philippines ■Collaborations in the future• Enhance local and international public-private partnerships
CTTO• Streamline database and registries for public and private
research• Create public awareness regarding research and clinical trials• Encourage health professionals to attend international
conferences• Increase capacity building• Focus on translational research• Participate more in global trials© 2018 National Center for Global Health and Medicine

CTTO

25
25

Thank you for your kind attention!
CTTO© 2018 National Center for Global Health and Medicine

26
26Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201953

3. Clinical Trials in Viet Nam: Current Situation and Challenges
Nguyen Chinh Dai / Ngo Thi Phuong Nhung

BACH MAI HOSPITAL

CLINICAL TRIALS IN VIET NAM
Current situation and challenges
Nguyen Chinh Dai, CRH
Ngo Thi Phuong Nhung, BMH

1

4- Founded in 1911, beginning a small contagious hospital as be know
with the name is Cong Vong

Brief introduction about Bach Mai Hospital(BMH), Cho Ray Hospital (CRH)

In 19112

2

5Over its 100 years history, Bach Mai has now become a leading
comprehensive general hospital with spacious facilities, synchronizedmodern equipment and qualified staffs.

Ho Chi Minh
City

3

54

6

｜別添 5 / Apendix 5 ｜ 3.

Clinical Trials in Viet Nam: Current Situation and Challenges ■Daily activities
About:• 200 emergency patients• 5.400 out-patients• 4100 in-patients

Training

7

10

Nowadays, Bach Mai Hospital has become one of the largest hospitalin Viet Nam. It has over 3000 beds with:

1. International cooperation
Collaboration (bout training, lecture,research,…) with internationalorganizations in many countries: US (CDC,
Washington University, Harvard,..), UK(Oxford,..), Japan (JICA, Nagasaki
University, NCGM,..), Sweden (Karolinska
Institute, Upsala University,…), Germany,
France, Taiwan, …
2. Science research: all of fields- In the hospital- In the country- International: about drugs, diseases,…We have been participating in 20
clinical trials, mostly about cancer
drugs, hepatitis C drugs, antiviraldrug,..

3 Institutes
10 Centers

23 clinical Departments

12 Functional
Departments

6 Paraclinical
Departments
1 Bach Mai
MedicalCollege School

8-

Missions:
Treating patients
Teaching medical
students, post
graduates
Scientific research& International
cooperation
Training &Direction ofhealthcare

Moderntechniques

ECMO

11

CHO RAY HOSPITAL
Robotic surgery

The top referral hospital of the 37 southern provinces, serves a
Stem cell transplant

total population of 40 million.

Kidney transplant

912Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 2019

55

MISSIONSTreating patients from the southern provinces of Vietnam
Teaching medical students and post graduates from both local
and international institutions

1900
Hôpital Municipal de Cho Lon

Undertaking scientific research & directing first line treatment in
the region

1957
Choray hospitalInternational cooperation
Hospital autonomy in health economics

13

16

5 Centers

Area 55.000 m2

Training & DOHA
Blood transfusion
Oncology
Cardio-vascular1971 -1974: Constructed new hospital with
grant aid from Japan’s government

DI & ADR

14

17

36 Clinical
Departments

09 Paraclinical
Departments
11 Functional
Departments

Six Sigma certificate

ISO 15189:2012 Medical Testing Laboratory

3200 beds

15

56

18

｜別添 5 / Apendix 5 ｜ 3.

STAFF

CLINICAL TRIALS IN VIET NAM

Staff 3940

Doctors
Nurses872
1668

Technicians
Pharmacists

400
96

Others904

Clinical Trials in Viet Nam: Current Situation and Challenges ■https://clinicaltrials.gov/ct2/search/map?map=SE

19

22

CLINICAL TRIALS IN VIET NAM

Daily activities
350 emergency patients
5.500 out-patients
2700 in-patients/day

Vaccine10%2014

2.700 in-patients

2015

2016

PERCENTAGE OF CLINICAL TRIALS
Other
Oncology
11%
13%
HIV
9%

Diabetes
6%
Heart disease3%

150 surgeries

2013

22

Lung Disease
13%

Infectious
Disease
35%

2017

23

20

23

List of hospitals able to handle clinical trials
in Viet Nam

Current situation and challenges ofclinical trials in Viet Nam

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.

21

Cho Ray Hospital
Nguyen Tri Phuong Hospital
Hospital for Tropical Diseases
115 People Hospital
University Medical Center HCMC
Children’s Hospital 1
Children Hospital 2
Gia Dinh People Hospital
Pham Ngoc Thach Hospital
Cancer Hospital in HCM City
Heart Institute of HCM City
Tam Duc Hospital
Pasteur Institute in HCMCCan Tho General Hospital Central
Tu Du Hospital

1. Bach Mai Hospital
2. 103 Hospital
3. National hospital of Tropical Diseases (NHTD)
4. K Hospital (Oncology)
5. Hanoi Heart Disease
6. 108 Hospital
7. National Hospital of Lung Disease
8. Viet Duc Hospital
9. National Hospital of Obstetrics and Gynecology
10. National Geriatric Hospital
11. Hanoi Medical University Hospital
12. National Institute of Hygiene and Epidemiology
13. National Institute of Malariology, Entomology and Parasitology
14. Thanh Nhan Hospital1.

Hue Central Hospital

2.

Da Nang General Hospital

24

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201957

SCIENCE RESEARCH DEPARMENT

CLINICAL TRIAL IN VIET NAM• Submission of product dossier• DUTY:– Submission of a product dossier and the clinical trial
protocol to the Administration of Science, Technology andTraining of the Ministry of Health comes after approval of
the application dossier.
– Upon receipt of the product dossier, two examinations are
conducted. The first by the Science and Technology Council
and the second by the Biomedical Research Ethics Council.
Both are within the Ministry of Health– Manage: Research, Clinical Trials of International
pharmaceutical company, Research of medical
students and specialist doctors– Establish: Institutional Review Board, Ethics
council.
Business Use Only

25

Business Use Only

25

CLINICAL TRIAL IN VIET NAM

28

CLINICAL TRIAL IN VIET NAM• Submission of product dossier(cont)– As the importance of biomedical research grows in
Vietnam, the government's scientific and ethicalstandards have become more stringent in an effort toprovide a more comprehensive regulatoryenvironment.
– Simultaneously, the Vietnam Ministry of Health isworking to expedite the regulatory approval process
for clinical trials by providing comprehensive
instructions on the requirements for documentation
Business Use Only

– The Science and Technology Council considers thescientific basis of the proposed trial, while the Biomedical
Research Ethics Council examines the ethical aspects of theclinical trial.
– Based on the results of these examinations, the Scienceand Training Department will request further
supplementary documents if it deems the product dossier
information to be insubstantial. If results are positive, itwill forward the results to the Minister of Health forapproval

26

Business Use Only

26

CLINICAL TRIAL IN VIET NAM

29• Requirements and conditions– Any investigating organizations seeking the registration ofclinical trials must have qualified facilities, equipment andhuman resources to comply with Good Clinical Practice(GCP).
– Only central level health institutes the Vietnam Ministry of
Health directly manages are eligible to conduct clinical
trials. Provincial level health institutes are only allowed to
conduct clinical trials in Ho Chi Minh City– Registration of a clinical trial requires the submissionof a complete application dossier with the
Administration of Science, Technology and Training of
the Ministry of Health. The Ministry of Healthresponds within 15 working days with an approval
letter, allowing the investigating organization to takenext steps, or rejects the application.
27

27

58

29

CLINICAL TRIAL IN VIET NAM• Submission of application dossier to register aclinical trial

Business Use Only

28

Business Use Only30

30

｜別添 5 / Apendix 5 ｜ 3.

CLINICAL TRIAL IN VIET NAM

CLINICAL TRIAL IN VIET NAM• Requirements and conditions(cont)– All participation in clinical trials must be voluntary.
Informed consent must be given by participants. Ifchildren, the mentally disabled, people living with
HIV/AIDS, pregnant women and others withspecial conditions wish to volunteer for clinical
trials, the Minister of Health must give consent
firstBusiness Use Only

Clinical Trials in Viet Nam: Current Situation and Challenges ■31

31

CLINICAL TRIAL IN VIET NAM

OPPORTUNITIESCHALLENGERS• Large amount of patients.
• Skilled doctors.
• Low cost (patients andinvestigations).
• Well equipped facilities.

• Long time startup.
• Public ResearchInformation.
• Self report of patients.
• Non treatment adherence.

Business Use Only

34

34

THANK
YOU!!!
THANK YOU AND
HAPPY
LUNAR NEW YEAR!!!

• The advantages of clinical trials in Vietnam– Vietnam's large population is treatment-naïve, providing avast pool of participants with diseases from both thedeveloped and developing world at a rapid pace for clinical
trials. Doctor -patient relationships are strong in Vietnam,
and as a result, the retention rate for clinical trials is high.
– Furthermore, a new law has been implemented by the
National Assembly of Vietnam. In previous years, newforeign medicines had to go through clinical trials in theirnative countries before being circulated in Vietnam forfurther testing
Business Use Only

32

35

32

35

CLINICAL TRIAL IN VIET NAM• The advantages of clinical trials in Vietnam– Under the new law, effective from January 1, 2017,
this time- and resource-consuming requirement has
now been waived (if the appropriate clinical data to
support a medication's safety and efficacy can beprovided).
– The new law allows Vietnam to focus its time andresources on important clinical trials more efficiently
Business Use Only

33

33
Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201959

4. Clinical Trials on Public Institutions in Indonesia
Anggi Gayatri / Nina Mariana

Top 10 causes of disease burden in 2016
1. Ischemic heart disease
2. Stroke
3. Diabetes
4. Tuberculosis
5. Low back and neck pain
6. Neonatal preterm birth complications
7. Sense organ diseases
8. Road injuries
9. Skin diseases
10.Diarrheal diseases

Clinical trial
on public institutions in Indonesia
Nina Mariana
Anggi Gayatri

On the road to universal health care in Indonesia, 1990–2016: a systemic analysis for the Global Burden of Disease Study
2016, The Lancet

1

Indonesia

4

The main causes of burden diseases in Indonesia
2010

NCD
63%

• Total population à ± 265 millions

2013

Com
muni
cable
28%

injuri
es
9%

NCD
71%

Com
munic
able
22%

Injuri
es
7%

2016

NCD
73%

Com
munic
able
21%

Injuries
6%

Double burden diseases & NCD WHO country profile
MoH of Indonesia

2

5
5

2

The Challenges

SULIANTI SAROSO
NATIONAL
INFECTIOUS
DISEASES HOSPITAL(SS-IDH )DEPARTMENT OF
PHARMACOLOGYAND THERAPEUTICS
FACULTY OF
MEDICINE,
UNIVERSITASINDONESIA

1. Infectious diseases (unfinish)
2. New emerging infectious diseases
3. Evolution from communicable –noncommunicable diseases

3à NCDs are increasingly important while
infectious diseases remain a significant partof the diseases burden

6
6

60

｜別添 5 / Apendix 5 ｜ 4.

Clinical Trials on Public Institutions in Indonesia ■DOTS TB & MDR
TB

Number of HIV-AIDS cases in Indonesia
32,711
29,03730,93527,963

21,591 21,031 21,511

10,862

10,362 9,793
7,195
5,239

6,048

3,680

4,828

5,298

6,744

7,470

11,741

8,279

7,963

7,185
3,679

859

s.d. 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016*
2005
Jumlah Kasus HIV
Jumlah Kasus AIDS

Source: report of counseling service, HIV test and AIDS surveillance

7

7

TB
Absolute
incidence rate

MDR TB% totalglobalNumber of MDR
TB case% totalglobal

1

India

22.7

India

23.7

2

Indonesia

10.3

China

17.3

3

China

9.6

Russian Fed.

13.0

4

Nigeria

5.9

Ukraina

4.3

5

Pakistan

5.2

Pakistan

4.0

6

Afrika selatan

4,8Philippines

3.7

7Banglades

3,7

Myanmar

3.0

8

Filipina

3

Uzbekistan

2.3

9

DR Kongo

2,5Indonesia

2.3

10

Etiopia2,1

Afrika Selatan

2,1

10

National referral for ERID;

TB incidence, Top Ten Countries, 2014
No

10

Variation cases of emerging infectious
diseaseincluding
Underinvestigation Mers-CoV,
H5N1, H1N1, H3N1 confirm,
Ebola suspect,
Zika suspect, Diphteri, Rabies,
Meningoxocoma,
MDR TB;

Insulation room for airborne
transmission with WHO certified

8

SULIANTI SAROSO
NATIONAL INFECTIOUS DISEASESHOSPITAL(SS-IDH )HIV Clinic

11

Facilities of Research Services …

Biological material Storage Facilities

Freezer 80°C
9

9

units

Fridge -20°C
units

Refrigerator
4°C units

12

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201961

Biomolecular Laboratory

Examples of Research Activities

1313

1. A FIRE study : Acute Febrile Illness Study
2. PROACTIVE Study : prospective, observational
cohort study of HIV positive antiretroviral-naïve
and treatment – experienced individuals
3. AMR study
4. The Study plan: A Randomised Control Trial To
Evaluate Efficacy and Safety of Rifampicin 8
mg/kg/day and 12 mg/kg/day For Pulmonary
Tuberculosis

16
16

Clinical trial in Faculty of Medicine,
Universitas Indonesia

Monitoring Laboratory for Clinical Research

14

14Collaboration

17

17

DEPARTMENT OF PHARMACOLOGY AND THERAPEUTICS
FACULTY OF MEDICINE, UNIVERSITAS INDONESIA• NCGM• INA-RESPOND : a multi-centre clinicalresearch network in Indonesia
à 7 medical faculties
à 9 corresponding hospitals
à Eijkman institute• Main activities– Teaching– Research• Research

15
15

62

Source: www.clinicaltrial.gov– Operational research à related to teaching
hospital (Cipto Mangunkusumo hospital,
Persahabatan hospital, etc)
– Biomedical research à in vitro and in vivo trial– Clinical trial
18

18

｜別添 5 / Apendix 5 ｜ 4.

Clinical Trials on Public Institutions in Indonesia ■DLBS 1033 (Lumbrokinase)

Clinical trialàbioactive protein fraction, extracted fromgastrointestinal system of Lumbricus rubellus• Chemical medicine– Antimalarial for Plasmodium vivax• Herbal medicine– Oral VCO (virgin coconut oil) for mild dyslipidemia– “Buah Merah” to decrease blood glucose– Lumbrokinase (extracted from earthworm) as fibrinolysis
agent• Cosmetics product– Sunscreen– Topical VCO for anticellulite– Topical vitamin C (on going research)

19• Developed by Dexa Medica company (National
pharmaceutical industry in Indonesia)• Origin of earthworm à Pengalengan, West of Java
• Tablet à 490 mg enteric coated tablet• In vitro study (by Trisina et al)– fibrinogenolytic & fibrinolytic activity– Inhibition of platelet aggregation– Prolong clotting time

19

22
22

Collaboration

Study objectives• Eijkman institute• CRSU (Clinical research study unit) at FMUI• Clinical department at RSCM hospital• Oxford university• To investigate the impact of DLBS1033– on fibrinolytic system à PAP complex, fibrinogen– on coagulation system à PT and aPTT
– antiplatelet effect à platelet aggregation– safety profile of DLBS1033 à creatinine, AST and
ALT serum

Ethics committee• Since 1990
• 19 reviewer from variation fields à with GCP
certificate• 4 administration staffs
20

20

23
23

Study design
THE IMPACT OF DLBS1033(LUMBROKINASE) ON FIRBINOLYTIC
SYSTEM IN HEALTHY VOLUNTEER• Sponsored by à Dexa Medica company• Double blind, randomized, cross-over study (1week wash out period)– Compare to placebo• Pilot study à 20 healthy subjects• Drug administration à 3 x 490 mg/day for 1
week

DEPARTMENT OF PHARMACOLOGY AND THERAPEUTICS
FACULTY OF MEDICINE, UNIVERSITAS INDONESIA

21

24
24

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201963

PAP complex
Parameter

Platelet aggregation

Study drug

Placebo% changes(mean ± SD)% changes(mean ± SD)

PAP complex (ng/mL)

66,7 ± 133,13

8,8 ± 108,15

0,07 (NS)(-5,34) – 121,09

ECLT (menit)-6,25 ± 28,99-4,1 ± 25,54

0,804 (NS)(-19,91) – 15,64

Fibrinogen (mg/dL)

0,4 ± 14,91

2,5 ± 18,40

0,729 (NS)(-15,1) – 10,76

Agregasi trombosit-16,3 ± 26,18

3,9 ± 26,15

0,032*(-38,43) – (-1,98)

Increased of plasminogen
PT (detik)-0,6 ± 3,53
-0,7 ± 2,43
activation(%)

aPTT (detik)

0,6 ± 3,97p

95% CI
Parameter

Not significant

0,0 ± 3,66

Study drug

Placebo% changes(mean ± SD)% changes(mean ± SD)

PAP complex (ng/mL)

66,7 ± 133,13

8,8 ± 108,15

0,07 (NS)(-5,34) – 121,09

Fibrinogen (mg/dL)

0,4 ± 14,91

2,5 ± 18,40

0,729 (NS)(-15,1) – 10,76

Platelet aggregation-16,3 ± 26,18

3,9 ± 26,15

0,032*(-38,43) – (-1,98)

0,904 (NS)(-2,03) – 2,28

PT (detik)-0,6 ± 3,53

-0,7 ± 2,43

0,904 (NS)(-2,03) – 2,28

0,691 (NS)(-2,5)– 3,69

aPTT (detik)

0,6 ± 3,97

0,0 ± 3,66

0,691 (NS)(-2,5)– 3,69

DLBS1033 could be used
as antiplatelet

25

PAP complex (ng/mL)

Placebo% changes(mean ± SD)% changes(mean ± SD)

66,7 ± 133,13

8,8 ± 108,15

28

28

Fibrinogen
Study drug

95% CI(%)

25

Parameterp

Safety parameterp

95% CI

Parameter
0,07 (NS)Fibrinogen (mg/dL)

0,4 ± 14,91

2,5 ± 18,40

0,729 (NS)(-15,1) – 10,76

Agregasi trombosit-16,3 ± 26,18

3,9 ± 26,15

0,032*(-38,43) – (-1,98)

PT (detik)-0,6 ± 3,53

-0,7 ± 2,43

0,904 (NS)(-2,03) – 2,28

aPTT (detik)

0,6 ± 3,97

0,0 ± 3,66

0,691 (NS)(-2,5)– 3,69(%)

No changed on
fibinolysis activity

Study drug
Before(-5,34) – 121,09

After

Placebo
beforeafter

AST

22,5 ± 6,46

21,6 ± 5,97

23,1 ± 5,93

22,7 ± 8,47

ALT

25,4 ± 13,84

24,7 ± 13,98

27,7 ± 16,80

27,8 ± 19,69

Creatinine

0,9 ± 0,110,9 ± 0,10

0,9 ± 0,10

0,9 ± 0,12

• Study drug do not have impact on liver and renal function• There were no serious adverse event
26

26

29
29

PT & aPTT
Parameter

Conclusion of lumbrokinase trial

Study drug

Placebop

95% CI% changes(mean ± SD)% changes(mean ± SD)

PAP complex (ng/mL)

66,7 ± 133,13

8,8 ± 108,15

0,07 (NS)Fibrinogen (mg/dL)

0,4 ± 14,91

2,5 ± 18,40

0,729 (NS)(-15,1) – 10,76

Agregasi trombosit-16,3 ± 26,18

3,9 ± 26,15

0,032*(-38,43) – (-1,98)

PT (seconds)-0,6 ± 3,53

-0,7 ± 2,43

0,904 (NS)(-2,03) – 2,28

aPTT (seconds)

0,6 ± 3,97

0,0 ± 3,66

0,691 (NS)(-2,5)– 3,69(-5,34) – 121,09(%)

DLBS1033 did not impact on
coagulation system27

27• Effect of DLBS1033 (Lumbrokinase) on healthy
subject:– No significant impact on increasing
fibrinolysis activity– No impact on coagulation system– Decreased platelet aggregation significantly– No impact on liver and renal system
function, and no serious adverse event
30
30

64

｜別添 5 / Apendix 5 ｜ 5.

Clinical Trials: Current Situation and Challenges in Thailand ■5. Clinical Trials: Current Situation and Challenges in Thailand      Borimas Hanboonkunupakarn / Boonjing Siripaitoon

Axe and axe
handlemap shape

Clinical Trials: Current situationand challenges in Thailand
Boonjing Siripaitoon
Division of Allergy & Rheumatology, Prince of Songkla University

Borimas Hanboonkunupakarn
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University

1

4

Q1. Current situation of clinical trials

Outline1. Introduction to Thailand
2. Current situation of clinical trials in Thailand
3. The health problems that our country is facing
4. What can be done to make our collaboration more
efficient in the future?

Japan
Southeast Asia

https://clinicaltrials.gov/ access date 18 Jan 2019

2

5

3

6

ThailandComprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 2019

65

7

10

8

11

What is Thailand 4.0 National Plan?

Thailand 4.0 is an economic model that aims to unlock thecountry from several economic challenges resulting from pasteconomic development models.
Source from https://thaiembdc.org/thailand-4-0-2/

Executive summary from prema , http://www.prema.or.th/www/en/images/publications/1.pdf (access date 18 Jan 2019)

9

66

12

｜別添 5 / Apendix 5 ｜ 5.

Clinical Trials: Current Situation and Challenges in Thailand ■Q2. The health problems that our country is facing?

• The SWOT analysis found the most important factors for attracting
foreign clinical trial investment to Thailand are the large treatmentnaïve patient population and the highly skilled workforce.
• The lengthiness of the independent ethical approval process and theimport license approval process were considered the biggest
impediments to increased foreign investment in clinical research.

http://www.healthdata.org/thailand Accessed on 22 Jan 201913

16

The procedure of IND review in Thaland
IND submission

IND approval
Conduct clinical trial

IRB/EC submission

IRB/EC approval

20 working days for non-phase 1 of chem
60 working days for bio, herbal, vet med, all phase 1
Satita Tonsakulchaisanti, Thai FDA

1417

Q3. What can be done to make our collaboration
more efficient in the future?
1. Trainings and seminars to improve MRCT operation and quality
2. Investigator meeting
3. Country representatives will cooperate/connect to NCGM to conduct MRCT if
capable, or to facilitate searching the potential investigators in the special
disease areas, and also guide the more efficient clinical trial operation/ trial
submission through local regulation
4. Connection between Individual CRC (Clinical Research Center) or MedResNet
in Thailand and NCGM would help in searching the potential investigators inspecial areas and cooperation in conducting MRCT
5. MOU between NCGM with academia or CRC in university hospitals ofThailand for cooperation in conducting MRCT

15

18

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201967

Current projects with international collaboration

Joint MORU research activities• Phase I and II trials of antimalarial drugs• Pharmacokinetic interactions between primaquine and major bloodschizontocides.

19

Tracking Resistance to Artemisinin Collaboration (TRAC study)
TRAC I (2011-2013)

22

Thank you for your attention

Location of Study Sites andProportions of Patients with
Artemisinin Resistance (red pie).

n= 1241, 15 sites in 10 countries

Artemisinin resistance; PCT1/2 >5 h, with kelch13 polymorphisms(at or beyond amino acid position
441).
Ashley et al, N Engl J Med
2014;371:411-423.

20

TRACII (2015-2018)
A multi-centre, open-label
randomised trial to assess theefficacy, safety and tolerabilityof Triple Artemisinin-based
Combination Therapies(TACTs) compared to
Artemisinin-based
Combination Therapies (ACTs)
in uncomplicated falciparum
malaria and to map thegeographical spread ofartemisinin and partner drug
resistance

21

68

23

Comprehensive and collaborative training on medical innovations adapted to challenges of clinical trials in Asian and African countries | Jan.16-25, 201969

Comprehensive and collaborative training
on medical innovations
adapted to challenges of clinical trials
in Asian and African countries
発行 / Issue
令和元年 5 月
May, 2019
国立国際医療研究センター
臨床研究センター
インターナショナルトライアル部
National Center for Global Health and Medicine
Center for Clinical Sciences

Department of International Trials

1-21-1 Toyama Shinjuku-ku, Tokyo, Japan 162-8655
Tel ： +81-3-6228-0445 / Fax ：+81-3-6228-0486
E-mail ： dit-info@hosp.ncgm.go.jp

NCGM website：http://www.ncgm.go.jp/

Department of International Trials website ：http://ccs.ncgm.go.jp/050/index.html