跨國醫學研究的倫理 -- 以所羅門為例

高雄醫學大學葛應欽教授

2007.10.12於台灣生命倫理學會

跨國醫學研究的倫理--以所羅門為例

Ethics in international biomedical research:

1.Health

2.Medicine

3.Genetics

questionnaires

specimen(blood, urine…)

basic medicine

clinical medicine

traits

diseases

International ethical guidelines for biomedical research involving human subjects (1993)

“ Council for International Organization of Medical Sciences (CIOMS), which, in collaboration with WHO”

Revision of Helsinki Declaration (1999)

1. Distinction between “therapeutic” and “non-therapeutic” research

2. The use of placebos

人類基因體計畫於 2003 年宣佈基因體定序完成，也代表著後基因體時代的來臨。

遺傳流行病學遺傳流行病學重要任務重要任務

找出功能性基因及與環境因子之交互作用並由此開發藥物或提供治療的模式預防 (prevention)

預測 (prediction)

保護 (protection)

Biobank Biobank 之建立之建立從單一個體的研究轉變成對整個族群的研究。

基因資訊本身的價值必須結合個人的健康醫療紀錄、生活型態、及家譜等相關資料，才能藉由關連研究 (association study) 、連鎖分析 (linkage study) 等技術來尋找出醫療相關的重要知識，這也是未來個人化醫療 (personalized medicine) 所要發展的方向。

它可以提供：（ 1 ）族群基因資料庫（ 2 ）遺傳背景的結構與遺傳物質儲存及提供庫（ 3 ）測定特定基因或變異型在特定族群的差異性（ 4 ）尋找生物標記，並進一步應用於新藥抑制、代謝或是檢測工具研發（ 5 ）藥物基因體學的研究基礎（ 6 ）預測族群內危險基因因子 , 助益預防醫療（ 7 ）國家公共衛生、福利、保險及社會政策依據等。

衍生之倫理道德與法律問題衍生之倫理道德與法律問題資料管理及運用的管制若沒有良好的機制加以管理，無限上綱形式的學術研究，將可能侵犯個人隱私權，甚至衍生個人或群體的生存權及工作權之爭議。

基因研究所產生的資料的管理及防火牆機制，甚而推及到後續產生的商業價值及相關應用，都亟需成立專案辦公室，以公平、公正、公開的方式訂出推動的標準文件來釐清所有可能引起爭議或任何侵犯人權的議題。

ELSI 問題現有法規基礎(1) 醫學研究倫理委員會 (IRB)

(2) 知情同意書特殊法規(1) 小規模單一之研究(2) 大規模之族群研究(3)Biobank 之建立

倫理法規檢討：倫理法規檢討：

醫療機構人體試驗委員會組織及作業基準研究用人體檢體採集與使用注意事項醫療法 - 有關保密條文相關醫事人員法規告知同意程序及注意事項同意書格式等。

關鍵概念本計劃應遵循的基本理念或原則

隱私權與保密整個建置的過程不論在檢體蒐集、儲存、接取、管理以及應用以及後

續的營運監督，都應建立相關之規範或準則（protocol），並就維護

confidentiality 之需求，建構相關之治理與監督機制，並規劃國家層

級的倫理架構。

知情同意與撤銷

（個人與群體）

依據 UNESCO之要求，在基因資料庫建置過程中所需之 consent為

“Prior, free, informed and express consent, without inducement

by financial or other personal gain” 準此，在建置台灣的族群基因

資料庫過程中，如何重視不同情境下的 consent程序需求，並配合資

料庫所徵求參與者之屬性，設計完整的諮詢機制，並於群體或社群參

與的情形下，整合具有社區營造經驗的全國性社團、原住民醫學會、

相關病友團體或其他特殊族群，與之協力建構能滿足台灣特殊需求的

group consent機制。

退出機制的設計必須以尊重參與者的自主空間為前提，兼顧參與者的

參與程度及進程，以及斟酌科學研究的完整性，來加以設計。

公共資源化在資料庫的接取與使用或應用上，應強調資料庫之公共資源化，並建

構符合倫理機制之資訊擴散管理架構，其中包括科學與倫理的審查機

制，以及國內學研機構的公平使用機會。

資料庫的使用應以公益使用為原則，若有從事商業應用之必要，則應

透過符合倫理、社會共識以及公平回饋的原則，透過妥適的公眾利益

監督機制來進行；基此，政府並應建立全國性倫理機構與治理架構來

落實其願景目標。

公益使用資料庫的使用應以公益使用為原則，若有從事商業應用之必要，則應

透過符合倫理、社會共識以及公平回饋的原則，透過妥適的公眾利益

監督機制來進行；基此，政府並應建立全國性倫理機構與治理架構來

落實其願景目標。

政府並應考慮就資料庫之使用與應用，制定完善法規與作業準則規範

之；其中並應積極考慮制定維護民族基因資訊安全之法規。

推動台灣族群基因資料庫的基本原則推動台灣族群基因資料庫的基本原則

推動台灣族群基因資料庫的基本原則推動台灣族群基因資料庫的基本原則關鍵概念本計劃應遵循的基本理念或原則

無歧視性在與基因資料庫相關之研究部分，其方法與目的，均應遵循非歧視性

原則，尤其在參與者之篩選以及避免污名化部分，應特別重視參與之

篩選與研究方法及目的性之間的關聯性，並應特別斟酌台灣現實研究

會傾向採行的三種人口界定方式；即

一般人口群：屬於一般篩檢或普查的範疇

族群為基礎的人口群：如閩南、客家、與不同族群的原住民

特殊基因為基礎的人口群：如某種病友團體及其支持親屬網絡

利益分享在不違背 UNESCO的利他(altruism)原則下，應重視參與者因執行本

案所得以主張或享有之利益分享權益。

其分享原則與方式應本諸於公益、非個人之精神，且應本諸科學研究

對於 tissue、DNA及 DNA information之法律屬性認知，並綜合考

量由生物統計學、財務精算、與風險評估等不同的專業觀點，依據不

同實驗設計與疾病因子的成本效益和風險考量，來設計出符合公平正

義的利益回饋機制。

公眾溝通與共識政府及研究單位應建立常態性的資訊與諮詢機制，並妥善培訓參與計

劃的研究相關輔助人員，以確立公眾，含專業與非專業與政府及研究

人員之間的溝通管道；其次，透過適當的社會溝通機制，如公民會議

或共識會議等，來強化資訊的透明度並促進社會的共識。

社會信任綜合國際間的經驗，本案的推動的成功關鍵將在於是否能順利取得應

有的社會信任，而政策與執行過程的透明度則是其核心，而為於台灣

而言，社區動員的能力，有其主動積極建立共識凝聚機制的功能，故

此，如何透過謹守政策透明化的原則來凝具社會的支持，將是根本性

的工作。

以英國經驗為例，獨立的國家倫理機構以及長期的社會觀察，是建立

社會信任的基礎。

基本人權執行計畫的過程應謹守不得以犧牲基本人權來換取研究利益的原則

品質保證透過查核與監督以維持基因庫品質。

前瞻性世代研究

重疊病例對照研究

連鎖分析

研究設計特徵 ELSI 問題

收集常人暴露不同環境與基因因子資料 , 追蹤疾病新發生之相關

收集新發生疾病病例 , 回溯其不同之環境與基因因子資料之相關

罹病兄弟或家族

20 萬人 / 總計

200-1000 對 / 每種疾病

家族之銘記

Biobank Biobank 提供基因醫學研究～提供基因醫學研究～研究方法研究方法

研究任何基因研究任何基因

易感基因複雜致病基因罕見疾病基因代謝基因保護基因訊號基因修復基因………..

ELSI 問題

(1) 有利或無利 ?

(2) 研究哪一種 ?

(3) 歸因比例 ?

(4) 成功案例 ?

已知基因部分已知基因候選基因候選位置未知基因

ELSI 問題

建立科學指導原則

須有倫理道德法律規範之依據

基因鑑定 ELSI問題

Genomics

SNP (Single Nucleotide Polymorphism)

100000-500000標記

STRT (Short Tandem Repeat Polymorphism)

新技術:

RNA-cDNA

Microarray

Array-CGH

CNV

Proteomics

Metabolomics

……

400-2000標記

?

研究何種疾病或遺傳特質？

Biobank Biobank 提供基因醫學研究～提供基因醫學研究～

南島民族之共同複雜疾病南島民族之共同複雜疾病1. 物質（酒、檳榔、菸）之過量使用

2. 糖尿病

3. 高尿酸血症及痛風

4. 肥胖

5. 高血壓、高血脂症

6. 肝硬化

7. 某些癌症：鼻咽癌、胃癌、口咽喉癌…

ELSI 問題是否將原住民健康問題納入研究範疇 ?

Biobank Biobank 提供基因醫學研究～提供基因醫學研究～參與者資訊來源參與者資訊來源

AGREEMENT ON COOPERATION IN HEALTH BETWEEN

THE MINISTRY OF HEALTH AND MEDICAL SERVICES, SOLOMON ISLANDS

AND THE DEPARTMENT OF HEALTH, EXECUTIVE YUAN

REPUBLIC OF CHINA（TAIWAN）

The Department of Health, Executive Yuan, Republic of China (Taiwan), and the Ministry of Health and Medical Services, Solomon Islands, hereinafter referred to as “the Parties”, desiring to improve the health of the peoples of Taiwan and the Solomon Islands, to promote mutual understanding and friendly relations, and to cooperate on medical services. Have agreed as follows: The Scope of this Agreement:

The Responsibilities of the Parties: Application of this Agreement: IN WITNESS WHEREOF the undersigned, being duly authorized by their respective Governments, have signed this Agreement. Done at Taipei, on the first day of December 2004 in duplicate in the English language.

Memorandum of Understanding for Research Collaboration

Under the 『Agreement On Cooperation In Health Between The Department Of Health, Executive

Yuan Republic Of China（Taiwan）And The Ministry Of Health And Medical Services, Solomon

Islands』（signed in 2004, as enclosure）.

1. Parties to the Memorandum

2. Agreement:

3. Programme Short Title:

4. Funding & Duration

5. Collaboration:

6. Proposed MHMS Solomon Role:

7. Proposed CAHD-NHRI Role:

8. Responsible presons for this Programme:

HEALTH RESEARCH ETHICS COMMITTEE, MINISTRY OF HEALTH

Solomon Islands

Ethics of Health Research in Solomon Islands: Executive Summary of Principles & Check List: Please answer (and demonstrate) the following questions: 1. Relationshps: To develop, cultivate and maintain principled

relationships is integral to all ethical practice: Demonstrate how you will build and maintain ethical relationships with the people studied?

2. Respect: The relationship between the researcher and the research participant is based on respect for the inherent value of each human being.

Kindly demonstrate the respect that will be gained and trust to the people studied.


Solomon Islands


Solomon Islands

3. Cultural competency: To practice in a culturally competent manner the researcher must have awareness of the people's own cultural beliefs, values and practices, and an awareness of these impact on the interaction with others.

How will you obtain ethnic specific and context specific (customs and conventions) of the people to be studied?

How will you communicate to the people or what language will you use?

4. Meaningful engagement: means consultation that goes beyond to form relationship that is sustained and maintained, ongoing and deepening.

Demonstrate you methods for effective consultation.


Solomon Islands

5. Reciprocity: Capacity building, reimbursement of time, accessible dissemination, benefits, and any financial gains from knowledge:

Demonstrate how you will provide for reciprocity from this research.


Solomon Islands

6. Utility: key objectives should be linked to improving health outcomes and where possible to ensure utility of the research:

Demonstrate how or lessons that such research will link.


Solomon Islands

7. Rights: Research should not be detrimental to the people, allow for rights and freedom to make informed choice. Risks inherent must be made clear to the people.

Demonstrate that rights of the people will be preserved as much as people: consent:


Solomon Islands

8. Balance: Who benefits from the research (reprocity): Balance in research in relationships and partnerships:

Demonstrate balance in research publications, potential commercial profit, training opportunities, and institutional capacity building:


Solomon Islands

9. Protection: Protection of Intellectual Property Rights (IPR). Primary knowledge (based experience and expertise) belongs to the people studied. Knowledge of indigenous safeguard.

Demonstrate that IPR is protected and there is readily accessible to all forms of research information and raw data:


Solomon Islands

10. Participation: Research targeting SI Populations entails participation of local staff al all levels of decision-making and implementation of the research project.

Demonstrate how you involve the local staff in the research.


Solomon Islands

11. Kindly demonstrate the following issues:

Who the researchers are What are the objectives of the research are The methodology of the research The type of knowledge that is being sought from him/her, whether

it is : -his/her opinion -knowledge about his/her lifestyle or the lifestyle of a

group of people -knowledge about cultural beliefs and practices -whether it is blood, DNA or any part of his/her body is

required.

How the knowledge will be used.

Who can access this knowledge

How can he/she access the results of the research?


Solomon Islands

SOLOMON ISLANDS GOVERNMENT MINISTRY OF HEALTH

NATIONAL REFERRAL HOSPITAL PO BOX 349, HONIARA, SOLOMON ISLANDS

Telephone: (677) 23600: Fax (677) 24243: e-mail: [email protected]

September 7, 2006

The Chairman Solomon Islands Research Ethics Committee, USHC MOH PO Box 349, HONIARA

Dear Cedric,

Re: Letter of Support for Collaborative Research between Taiwan National Health Research Institute and Solomon Islands I write to support Professor Ko’s request to do collaborative research in the area of Non Communicable Diseases in Solomon Islands. This is in line with the MOU signed previously by Dr Leafasia as PS copy attached. NCD as a group of diseases is on the rise in Solomon Islands as you well know. I will involve a number of young medical graduates who will participate in this research exercise to gain experience with doing research in the field. We are very fortunate that Professor Ko has shown an interest to help us understand a little bit more about our situation and the possible link between our genes and a number of factors relating to the risk factors for the diseases such as Gout, Diabetes Mellitus, Hyperlipidemia and so forth. I seek your favourable approval and an expedited reply to Professor Ko who will be leading the Volunteer Medical Delegation to the Solomon Islands from 19th September to 29th September 2006. Thank you.

Dr Silent Tovosia

Medical Superintendent

National referral Hospital

Informed Consent Human Ethics Committee

National Health Research Institutes

□√ Application of genomic patterns Permission Code： EC 0941203 We are inviting you to participate in the application of “Characterizing the genomic patterns of medically important genes and genomic regions in Austronesian populations”. Participation is entirely voluntary. Please read each sentence below and think about your choice. After reading each sentence, select "Agree" or "Disagree" and sign your name on the consent form if you decide to participate. No matter what you decide to do, this will not affect your care. If you have any questions, please talk to our research assistants or nurses, or call our research review board at IRB's phone number (886-37-246166 ext.33008). Title of this Application： Chinese：南島民族重要醫學相關基因之基因體各型態特徵 English：Characterizing the genomic patterns of medically important genes and genomic regions in Austronesian populations. Principle Investigator：Ying-Chin Ko Telephone No.：886-7-3114418 Sponsors：National Science Council (NSC) and National Health Research Institute (NHRI), Taiwan, ROC. Participant： Gender： Birthday： / / Communication address： Telephone No.： Mobile phone:

1. Purpose:

2. Methods and Procedures:

3. Potential risks and side effects:

4. Therapy choice and interpretation:

5. Expected results and benefits:

6. Protection issues:

7. Withdrawal:

8. Confidentiality: □Agree □Disagree

9. Signature: 9.1 The purpose and procedures have been explained to the participant as well as the potential risks and benefits. Principal Investigator Date: Collaborating Investigator Date:

Research Proxy Date:

9.2 I agree to participate in the research entitled “Characterizing the genomic patterns of medically important genes and genomic regions in Austronesian populations”, which is being conducted by the Principal Investigator Ying-Chin Ko and have the phone number where he can be contacted. I understand that this participation is entirely voluntary; I can withdraw my consent at any time and have the rights of the participation returned to me, removed from the experimental records, or destroyed. I have read and understood the potential risks and side effects during all processes.

Signature of participant：

Date：

If you are an agent of the participant,

please sign your name：

Date：

Also check the relationship between you and the participant.

□parent □guardian □spouse □adult child □attorney

□sibling □client (need to offer a warrant of attorney）□others.

Statement :

9.3 Signature of eyewitness ： Date：

建立科學指導原則

須有倫理道德法律規範之依據

須有群體與個別之共識及同意

結語結語

謝謝！！

跨國醫學研究的倫理 -- 以所羅門為例

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