ࡱ>  )`0pbjbj .{{h%___8``2ab"bbbccc$h)cc)bb>bb4uba !Z_v >LT0G.:|uu2cp 3py1]ccc))@dcccd6z<d#z<  DUQUESNE UNIVERSITY CENTER FOR HEALTHCARE ETHICS McANULTY COLLEGE AND GRADUATE SCHOOL OF LIBERAL ARTS COURSE HCE-654: RESEARCH ETHICS Fall 2015 (version March 2015) College: McAnulty College and Graduate School of Liberal Arts Syllabus: HCE-654, RESEARCH ETHICS, Fall 2015 Course: Tuesday 3:05-5:45 pm., Fisher Hall TBD Office hours: Appointment, Fisher Hall 300; Tel. (412) 396-4504 Email:  HYPERLINK "mailto:tenhaveh@duq.edu" tenhaveh@duq.edu Course instructor: Henk ten Have, M.D., Ph.D. Director and Professor, Center for Healthcare Ethics Duquesne University, 600 Forbes Avenue, Pittsburgh OUTLINE The course will make students familiar with the recent issues and debates in research ethics. It will start with the history of the debate on ethics and research (focusing on exemplary cases). It will analyze the various ethical dimensions of different types of research in the field of healthcare, in particular informed consent, risk-benefit assessment, ethical review, and research with special populations. It then offers the opportunity to study in more detail specific topics as international research, research with children, animal research, clinical data sharing, and pre-approval access. COURSE OBJECTIVES Course description. The course will make students familiar with ethical issues related to healthcare research. It will focus on the historical and ethical analysis of these issues. Starting from a historical analysis of major events in the development of medical research, the ethical dimensions of different types of research in healthcare will be studied. The focus will then be directed on several areas that are currently debated: international research, research with children, animal research, clinical data sharing (as an outcome of the movement towards global commons, discussed in the course on Global Bioethics), and pre-approval access to investigational drugs (previously known as compassionate use; currently know in the U.S. as the right to try legislation movement). Research competencies. Upon completion of the course students should master the following competencies, as should be demonstrated both in specific research projects and presentations, and in the research essay: Historical analysis of the present-day debate on research ethics, explaining why and how current research ethics has developed, as well as what ethical concerns have emerged and how these have been addressed and regulated; Systematic examination of fundamental ethical issues in relation to research, understanding and explaining how the contemporary debate is informed by fundamental interpretations of basic notions as informed consent, risk-benefit assessment and ethical review; Critical analysis of specific ethical debates and concerns regarding either international research, or research with children, or animal research, or clinical data sharing, or pre-approval access to investigational drugs. General HCE Program Learning Outcomes. Several of these Learning Outcomes pertain to HCE-656. Fundamental Knowledge. Students can understand and analyze HCE theory and methods as well as major applied topics in research ethics. Multi-disciplinary Study. Students can critically relate HCE with multi-disciplinary fields in health care, specifically in connection to the historical background and the ethical analysis of fundamental notions. Scholarship Students can research and write scholarly essays, teach and communicate effectively, and present academic papers that: present cogent arguments(s), engage scholarly literature, and demonstrate critical thinking and analysis. COURSE PROCEDURES. Course components The Fall semester will be divided into five components: Introduction of the course: 25 August. The program as well as main contents of the course will be clarified Research Project #1, week 1-5; prepare teaching presentation for Seminar #2, Sept.29 Research Project #2 (10 pages), week 6-9; due Friday October 23 for Seminar #3, October 27 Research Project #3 (10 pages), week 10-14; due Friday Nov.27 for Seminar #4, Dec.1 Research Essay (25 pages plus end notes & bibliography), weeks 12-15. Submit Essay thesis, 1-page outline, basic bibliography, Friday Sept.25. Option to submit mid-term essay. For students who want to be assisted in their progress, a draft of the essay can be submitted for feedback; by Friday Oct. 23. Submit Research Essay by Tuesday Dec. 9. Research projects Reading Requirements. Each Research Project will require students to critically engage the equivalent of 2 or 3 books to (a) master the relevant knowledge and (b) engage in critical reading and writing. Research competencies. The research competencies in the course are identified by the three Research Projects: (a) historical analysis, (b) systematic examination of fundamental ethical issues, and (c) ethical analysis of a specialized area of concern. Each Research Project will demonstrate that the student has mastered the specific competency. Relation of Projects with Essay. The three Research Projects may be integrated into the Research Essay but not in a manner of cut-and-paste from one to the other. The Research Essay typically demonstrates that the student can apply and integrate all three research competencies in relation to a specific topic or issue in research ethics. Projects: Research competency of historical analysis: Project: Teaching a case Study 10 cases in The Oxford Textbook of Clinical Research Ethics, chapters 1-10. Each chapter presents 1 case. Study 2 cases in Strangers at the Bedside, chapter 4 and 9. Make teams of 2 students selecting each 1 case. Each team selects a different case. Analyze the case and prepare a teaching presentation, addressing 3 questions: What are the significant aspects of the case? Why and how has the case had an impact on the development of research ethics? Can a case like this one happen again in todays healthcare research? Explain why or why not. Teach the case as a team in a mini-lesson of max. 10 minutes. Format: each team teaches the case in max. 10 minutes. Powerpoints or overheads may be used. Required Readings: David J. Rothman: Strangers at the bedside. A history of how law and bioethics transformed medical decision making. Basic Books, New York, 1991; 2003. Daniel Callahan: What price better health? Hazards of the research imperative. University of California Press (Berkeley, Los Angeles, London) and The Milbank Memorial Fund (New York), 2003; 2006. Ezekiel J Emanuel et al. (eds.): The Oxford Textbook of Clinical Research Ethics. Oxford University Press, Oxford/New York, 2008; Chapters 1-10 (pp. 9-120). Research competency of systematic examination of fundamental ethical issues: 10 Page Project: What makes research ethical, and how can the ethical quality of research be strengthened in todays society and culture? Format: 10 pages (double spaced; font 12) plus approximately 30 references/end notes Required Readings: Paul Oliver: The students guide to research ethics. McGraw Hill/Open University Press, Maidenhead, UK, 2010 (2nd edition). Ezekiel J Emanuel et al. (eds.): The Oxford Textbook of Clinical Research Ethics. Oxford University Press, Oxford/New York, 2008 (Chapters 11-15; pp. 123-167; Chapters 20-23; pp. 201-241; Chapters 24-25; pp. 245-272; Chapters 47-48; pp. 503-526; Chapters 55-59; pp. 591-660. Ruth Chadwick, Henk ten Have and Eric Meslin (eds.): The SAGE Handbook of Healthcare Ethics: Core and Emerging Issues. SAGE, Los Angeles, 2011 (Chapter 10; pp. 106-116; Chapter 20; pp. 239-250; Chapter 25; pp. 306-325. Research competency of ethical analysis of specialized areas of concern: 10 Page Project: What are the three most important ethical issues in your selected area? Explain: why are they important? how are they usually addressed? how can they be solved or eliminated? Format: 10 pages (double spaced; font 12) plus approximately 30 references/end notes Required Readings: Select 1 area of special concern: International research Research with children Animal research Clinical data sharing Pre-approval access to investigational drugs Select the requested readings for your selected area (see at the last pages of this Syllabus). Each area requires you to read 3 new books or the equivalent in publications that are outstanding in this area. There is no requirement to read the books for the specialized areas that you have not selected. Relevant information regarding your selected area can also be found in the general books used earlier in the course. Research Seminars. There will be four seminars introducing each of the three research competencies. Week 1. Seminar #1 to introduce Research Project #1 Introduction to the area of research ethics Discussion of research essay requirements Research Essay thesis and 1-page outline with basic bibliography to be submitted by end of week 3 Week 5. Seminar #2 to introduce Research Project #2 Discussion of progress on research essays Teaching presentations (10 minutes max) of completed Research Project #1 Week 9. Seminar #3 to introduce Research Project #3 Discussion of progress on research essays Discussion of completed Research Project # 2 Week 14. Seminar #4 to discuss the Research Essay Discussion of completed Research Project # 3 Brief presentations (8 min) of the research essays Research essay. The course research essay will require students to substantively apply the Course Research Competencies to a particular issue (theoretical or practical). Requirements: Start to reflect on the thesis of your research essay from the beginning of the course. Thesis and 1-page outline with basic bibliography to be submitted by the end of week 5 (Sept 25) (email to  HYPERLINK "mailto:tenhaveh@duq.edu" tenhaveh@duq.edu). You will receive feedback before and in Seminar #2. Progress will be reported in the subsequent Seminars. Each student will briefly present the research essay (max. 8 minutes) during the final Seminar and submit a copy of the essay by date assigned. The essay length should be 25 pages, double-spacing, font 12. Students must adopt the format of the Chicago Manual of Style, as required by the College for dissertation submissions. Select a research thesis that is the core of your essay, and is presented in the Introduction and reflected in the title of the essay. For example: Why is the notion of informed consent useful in international medical research, or Are waivers of informed consent ethically justified in the context of public health research? Present a brief Introduction (presenting the thesis) and Conclusion (summarizing how the thesis has been answered). Notes to the references made in the essay. Use end notes (as opposed to foot notes at the bottom of the page). Do not use notes for narrative explanations they belong in the main text. There should be approximately 100 end notes in the essay. Check Chicago Manual Style for correct presentation of notes. Bibliography. List all the references in alphabetical order. Only list items actually referred to in the essay. Check Chicago Manual Style for correct presentation of the literature references. Divisions and subdivisions. Use major divisions and subdivisions, evenly distributed throughout the essay, to lay out the sequence of concepts. Use of online references. Online references must be accurately identified with complete web address etc, including the date of access. HCE HANDBOOK. The Center for Healthcare ethics has developed a Handbook of Policies, Procedures, and Guidelines to guide students in all curriculum related matters. The Handbook is available on the website of the Center. COURSE GRADE. There will be no examinations. The course grade will be assigned based on the quality of the course research essay and the three research projects. The grade will be a combination of 10% for each of the three research projects and 70% for the final essay. No midterm grades will be assigned. End of term grades will be assigned adopting grading policy in the McAnulty College and Graduate School of Liberal Arts, as follows: A 4.0 distinguished scholarly work A- 3.7 B+ 3.3 B 3.0 normal progress towards degree B- 2.7 C+ 2.3 C 2.0 warning; student subject to departmental action F 0.0 ACADEMIC INTEGRITY. This syllabus incorporates the Expectations of Academic Integrity. Cheating and plagiarism cannot be tolerated. All relevant policies of the McAnulty College and Graduate School of Liberal Arts apply. REASONABLE ACCOMMODATIONS. Students with documented disabilities are entitled to reasonable accommodations if needed. If you need accommodations, please contact the Office of Freshman Development and Special Student Services in 309 Duquesne Union (412-396-6657) as soon as possible. Accommodations cannot always be granted retrospectively. COURSE READINGS HCE 654, Research Ethics, 2015 Fall Required reading: Books General texts for all students (all 5 books need to be read by all students): David J. Rothman: Strangers at the bedside. A history of how law and bioethics transformed medical decision making. Basic Books, New York, 1991; 2003. Daniel Callahan: What price better health? Hazards of the research imperative. University of California Press (Berkeley, Los Angeles, London) and The Milbank Memorial Fund (New York), 2003; 2006. Paul Oliver: The students guide to research ethics. McGraw Hill/Open University Press, Maidenhead, UK, 2010 (2nd edition). Ezekiel J. Emanuel et al. (eds.): The Oxford Textbook of Clinical Research Ethics. Oxford University Press, Oxford/New York, 2011 (the pages mentioned in the syllabus refer to the 2008 edition). Ruth Chadwick, Henk ten Have and Eric Meslin (eds.): The SAGE Handbook of Healthcare Ethics: Core and Emerging Issues. SAGE, Los Angeles, 2011. 2. Specialised texts depending on the area of practical application (following your choice of one area); here you only have to study the literature in your area of choice (for each area 3 books need to be read depending on your selected area). International research Ruth Macklin: Ethics and global health. Research, policy and practice. Oxford University Press, New York, 2011. Ruth Macklin: Double standards in medical research in developing countries. Cambridge University Press, Cambridge UK, 2004. Adriana Petryna: When experiments travel. Clinical trials and the global search for human subjects. Princeton University Press, Princeton and Oxford, 2009. Research with children Jonathon Sargeant and Deborah Harcourt: Doing ethical research with children. McGraw Hill/Open University Press, Maidenhead UK, 2012. Priscilla Alderson and Virginia Morrow: The ethics of research with children and young people. A practical handbook. SAGE, Los Angeles, 1995, 2011 (2nd edition). Lainie Friedman Ross: Children in medical research. Access versus protection. New York: Oxford University Press, 2006. Animal research Jeremy Garrett (ed): The ethics of animal research. Exploring the controversy. MIT Press, Cambridge MA, 2012 Vaughan Monamy: Animal experimentation. A guide to the issues. Cambridge, UK: Cambridge University Press, 2009 (2nd edition). Nuffield Council on Bioethics: The ethics of research involving animals. London, 2005 ( HYPERLINK "http://www.nuffieldbioethics.org/sites/default/files/The%20ethics%20of%20research%20involving%20animals%20-%20full%20report.pdf" http://www.nuffieldbioethics.org/sites/default/files/The%20ethics%20of%20research%20involving%20animals%20-%20full%20report.pdf) Susan Gilbert, Gregory Kaebnick and Thomas Murray (eds): Animal Research Ethics. Evolving view and practices. A Hastings Center Special Report, November-December 2012; 42 (6): S1-40. Clinical data sharing Institute of Medicine: Sharing clinical trial data: Maximizing benefits, minimizing risk. The National Academies Press, Washington DC, January 2015 ( HYPERLINK "http://www.nap.edu/openbook.php?record_id=18998" http://www.nap.edu/openbook.php?record_id=18998). Committee on Strategies for Responsible Sharing of Clinical Trial Data: Discussion Framework for Clinical Trial Data Sharing: Guiding principles, elements, and activities. National Academies Press, Washington DC, February 2015. Louise Corti, Veerle Van den Eynden, Libby Bishop and Matthew Woollard: Managing and sharing research data. A guide to good practice. SAGE Publication, London, 2014. Borgerson K: Redundant, secretive, and isolated: when are clinical trials scientifically valid? Kennedy Institute of Ethics Journal 2014; 24(4): 385-411. Rosenblatt M, Jain SH and Cahill M: Sharing of clinical trial data: Benefits, risks, and uniform principles. Annals of Internal Medicine 2015; 162(4): 306-7. Drazen JM: Sharing individual patient data from clinical trials. New England Journal of Medicine 2015; 372(3): 201-2. Knoppers BM, Harris JR, Budin-Ljsne I and Dove ES: A human rights approach to an international code of conduct for genomic and clinical data sharing. Human Genetics 2014; 133(7): 895-903. Pre-Approval Access to investigational drugs Lisa Forman and Jillian Clare Kohler (eds.): Access to medicines as a human right; Implications for pharmaceutical industry responsibility. University of Toronto Press: Toronto/Buffalo/London, 2012. Jonathan J. Darrow, Ameet Sarpatwari, Jerry Avorn and Aaron S. Kesselheim: Practical, legal, and ethical issues in expanded access to investigational drugs. New England Journal of Medicine 2015; 372(2): 279-286. Okie, S: Access before approval a right to take experimental drugs? New England Journal of Medicine 2006; 355: 437-440. Marks, GS: Expanded access rules pose quandary for drug developers. Nature Biotechnology 2009; 27: 871-2. Falit BP and CP Gross: Access to experimental drugs for terminally ill patients. JAMA 2008; 300: 2793-5. Leonard EW: Right to experimental treatment: FDA new drug approval, constitutional rights, and the publics health. Journal of Law, Medicine and Ethics 2009; 37: 269-279. Guidance for industry: expanded access to investigational drugs for treatment use. Rockvillee (MD), Food and Drug Administration, 2013 ( HYPERLINK "http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm351261.pdf" http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm351261.pdf). European Medicines Agency: Guideline on compassionate use of medicinal products, 2007 ( HYPERLINK "http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004075.pdf" http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004075.pdf) Mussa Rahbari and Nuh N.Rahbari: Compassionate use of medicinal products in Europe: current status and perspectives. Bulletin of the World Health Organization 2011; 89; 163-163. doi: 10.2471/BLT.10.085712 ( HYPERLINK "http://www.who.int/bulletin/volumes/89/3/10-085712/en/" http://www.who.int/bulletin/volumes/89/3/10-085712/en/) Research competency #1: Historical analysis David J. Rothman: Strangers at the bedside. A history of how law and bioethics transformed medical decision making. Basic Books, New York, 1991; 2003. Daniel Callahan: What price better health? Hazards of the research imperative. University of California Press (Berkeley, Los Angeles, London) and The Milbank Memorial Fund (New York), 2003; 2006. Ezekiel J. Emanuel et al. (eds.): The Oxford Textbook of Clinical Research Ethics. Oxford University Press, Oxford/New York, 2008. Chapters 1-10 (pp. 9-120). Research competency #2: Systematic examination of fundamental ethical issues in relation to research Paul Oliver: The students guide to research ethics. McGraw Hill/Open University Press, Maidenhead, UK, 2010 (2nd edition). Ezekiel J. Emanuel et al. (eds.): The Oxford Textbook of Clinical Research Ethics. Oxford University Press, Oxford/New York, 2008. Chapters 11-15 (pp. 123-167) Chapters 20-23 (pp. 201-241) Chapters 24-25 (pp. 245-272) Chapters 47-48 (pp. 503-526) Chapters 55-59 (pp. 591-660) Ruth Chadwick, Henk ten Have and Eric Meslin (eds.): The SAGE Handbook of Healthcare Ethics: Core and Emerging Issues. SAGE, Los Angeles, 2011. Chapter 10 (pp. 106-116) Chapter 20 (pp. 239-250) Chapter 25 (pp. 306-325) Research competency #3: Ethical analysis of specialized areas of concern International research Ruth Macklin: Ethics and global health. Research, policy and practice. Oxford University Press, New York, 2011. Ruth Macklin: Double standards in medical research in developing countries. Cambridge University Press, Cambridge UK, 2004. Adriana Petryna: When experiments travel. Clinical trials and the global search for human subjects. Princeton University Press, Princeton and Oxford, 2009. Ezekiel J. Emanuel et al. (eds.): The Oxford Textbook of Clinical Research Ethics. Oxford University Press, Oxford/New York, 2008. Chapter 16 (pp.168-173) Chapter 63 (pp.697-708) Chapters 64-67 (pp.711-744) Ruth Chadwick, Henk ten Have and Eric Meslin (eds.): The SAGE Handbook of Healthcare Ethics: Core and Emerging Issues. SAGE, Los Angeles, 2011. Chapter 26 (pp.326-341) Chapter 27 (pp.342-355) Research with children Jonathon Sargeant and Deborah Harcourt: Doing ethical research with children. McGraw Hill/Open University Press, Maidenhead UK, 2012. Priscilla Alderson and Virginia Morrow: The ethics of research with children and young people. A practical handbook. SAGE, Los Angeles, 1995, 2011 (2nd edition). Lainie Friedman Ross: Children in medical research. Access versus protection. New York: Oxford University Press, 2006. Ezekiel J. Emanuel et al. (eds.): The Oxford Textbook of Clinical Research Ethics. Oxford University Press, Oxford/New York, 2008. Chapter 42 (pp.446-460) Chapter 49 (pp.527-538) Chapter 60 (pp.661-669) Ruth Chadwick, Henk ten Have and Eric Meslin (eds.): The SAGE Handbook of Healthcare Ethics: Core and Emerging Issues. SAGE, Los Angeles, 2011. Chapter 22 (pp.261-277) Animal research Jeremy Garrett (ed): The ethics of animal research. Exploring the controversy. MIT Press, Cambridge MA, 2012 Vaughan Monamy: Animal experimentation. A guide to the issues. Cambridge, UK: Cambridge University Press, 2009 (2nd edition). Nuffield Council on Bioethics: The ethics of research involving animals. London, 2005 ( HYPERLINK "http://www.nuffieldbioethics.org/sites/default/files/The%20ethics%20of%20research%20involving%20animals%20-%20full%20report.pdf" http://www.nuffieldbioethics.org/sites/default/files/The%20ethics%20of%20research%20involving%20animals%20-%20full%20report.pdf) Clinical trial data sharing Institute of Medicine: Sharing clinical trial data: Maximizing benefits, minimizing risk. The National Academies Press, Washington DC, January 2015 ( HYPERLINK "http://www.nap.edu/openbook.php?record_id=18998" http://www.nap.edu/openbook.php?record_id=18998). Committee on Strategies for Responsible Sharing of Clinical Trial Data: Discussion Framework for Clinical Trial Data Sharing: Guiding principles, elements, and activities. National Academies Press, Washington DC, February 2015. Louise Corti, Veerle Van den Eynden, Libby Bishop and Matthew Woollard: Managing and sharing research data. A guide to good practice. SAGE Publication, London, 2014. Borgerson K: Redundant, secretive, and isolated: when are clinical trials scientifically valid? Kennedy Institute of Ethics Journal 2014; 24(4): 385-411. Rosenblatt M, Jain SH and Cahill M: Sharing of clinical trial data: Benefits, risks, and uniform principles. Annals of Internal Medicine 2015; 162(4): 306-7. Drazen JM: Sharing individual patient data from clinical trials. New England Journal of Medicine 2015; 372(3): 201-2. Knoppers BM, Harris JR, Budin-Ljsne I and Dove ES: A human rights approach to an international code of conduct for genomic and clinical data sharing. Human Genetics 2014; 133(7): 895-903. Pre-approval access to investigational drugs Lisa Forman and Jillian Clare Kohler (eds.): Access to medicines as a human right; Implications for pharmaceutical industry responsibility. University of Toronto Press: Toronto/Buffalo/London, 2012. Jonathan J. Darrow, Ameet Sarpatwari, Jerry Avorn and Aaron S. Kesselheim: Practical, legal, and ethical issues in expanded access to investigational drugs. New England Journal of Medicine 2015; 372(2): 279-286. Okie, S: Access before approval a right to take experimental drugs? New England Journal of Medicine 2006; 355: 437-440. Marks, GS: Expanded access rules pose quandary for drug developers. Nature Biotechnology 2009; 27: 871-2. Falit BP and CP Gross: Access to experimental drugs for terminally ill patients. JAMA 2008; 300: 2793-5. Leonard EW: Right to experimental treatment: FDA new drug approval, constitutional rights, and the publics health. Journal of Law, Medicine and Ethics 2009; 37: 269-279. Guidance for industry: expanded access to investigational drugs for treatment use. Rockvillee (MD), Food and Drug Administration, 2013 ( HYPERLINK "http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm351261.pdf" http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm351261.pdf). European Medicines Agency: Guideline on compassionate use of medicinal products, 2007 ( HYPERLINK "http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004075.pdf" http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004075.pdf) Mussa Rahbari and Nuh N.Rahbari: Compassionate use of medicinal products in Europe: current status and perspectives. Bulletin of the World Health Organization 2011; 89; 163-163. doi: 10.2471/BLT.10.085712 ( HYPERLINK "http://www.who.int/bulletin/volumes/89/3/10-085712/en/" http://www.who.int/bulletin/volumes/89/3/10-085712/en/) COURSE SCHEDULE Tuesday August 25. Seminar #1 Research competency #1: Historical analysis Project #1 September 1, 8, 15 and22, Research Project #1 Submit Essay Thesis, 1-page outline, basic bibliography, by Fri. September 25 Tuesday September 29. Seminar #2 Research competency #2: Systematic examination of fundamental ethical issues Project #2 October 6, 13 and 20, Research Project #2 Submit Project #2 by Fri. October 23 Optional: submit mid-term draft Research Essay, by Fri. October 23. Tuesday October 27. Seminar #3 Research competency #3: Ethical analysis of specialized areas of concern Project #3 November 3, 10, and 18; Research Project #3 Submit Project 3# by Fri. November27. Tuesday December 1. Seminar #4 Research essay Submit Research Essay by Tuesday, December 9.     PAGE  PAGE 1 4yz}~     ! ' ) - 2 3 : C zzvoh^zZSz hq/hthy#hq/hw5\ haBb5\ hq/hwhq/ hq/hq/hq/hq/>*haBbhaBb>*CJ$aJ$hPCJ aJ h:yCJ aJ h< CJ aJ haBbCJ$aJ$hbhaBbCJ,aJ,( *hbhaBbCJ,aJ,ehrhb haBbhaBbhaBbhaBbCJ0aJ0haBbhaBbhaBbCJ(aJ( haBb>*45opqrstuvwxyz{|}gdv&|gdaBb ^`gdaBbpp 3 b  L   & Fgd|h^hgdAD & Fgd GgdGRgdAD ^`gd$_gd$_gdq/C L P a b n }  0 @ o ҾҺ޶{q{fhCkhAD5\]hAD5>*\]hXhAD5>*\]hAD5>*\ hKyhk[hGRhk[hq/hAD5>*\h(5>*\hADhwhq/h[Ph$_0Jjh$_Ujh$_Uh[ hq/hq/h$_hq/hq/>*hb hq/hwhKy( : B f hl   !,]i Xƿ庵尺庵庫 hF\h NhAD>*\h|hF hGR\ hEA\ hb\ hKy\ h|\ hAD>*\ h|>*\h NhAD\h GhGRhKyhAD hAD\ hAD]h NhAD>*] h[>*]8ZfGHI\gdAD & FgdAD^gdAD^gdEA^gdF & FgdAD & FgdF8^8gdF & FgdGR & FgdEA & FgdKyp}1AXZfHIZ[\]nowz&02T`eg');ƾƮƪƦƪƪƪƚhs3hh[hbhy#hbhsZhFhAD>*hFhF>*hF hY/hADhADhY/hAD5>* hAD5>* hF\ hEA\h5whAD>*\ hAD\<\]oK>$ _P0p @ P !$`'0*-/2p5@8;=@CPF I1$^a$gdF<$ & F \P0p @ P !$`'0*-/2p5@8;=@CPF I1$a$gdF:$ _P0p @ P !$`'0*-/2p5@8;=@CPF I1$a$gdFh]K<$ & F \P0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gdb<$ & F \P0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gdv&|<$ & F \P0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gdb;WXZ[]=DK_mnoKLa)+>-./67GHZÿÿϺ hbhb h:y6]h:y hb6]h[h[h[>*h ~ hFNG>*h1e8h1e8h1e8>*hbhdh1e8hd>* hF>*hFhF>*hy#hhFh+Ihv&|hb7]FoN:$ & F YP0 P !$`'0*-/2p5@8;=@CPF I1$a$gdb:$ & F YP0 P !$`'0*-/2p5@8;=@CPF I1$a$gdv&|:$ & F YP0 P !$`'0*-/2p5@8;=@CPF I1$a$gdoLM:$ & F YP0p @ P !$`'0*-/2p5@8;=@CPF I1$a$gdb:$ & F YP0p @ P !$`'0*-/2p5@8;=@CPF I1$a$gdd<$ & F \P0p @ P !$`'0*-/2p5@8;=@CPF I1$a$gdF/P9$ & F VP0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gd1e8:$ & F YP0p @ P !$`'0*-/2p5@8;=@CPF I1$a$gdFNG:$ & F YP0p @ P !$`'0*-/2p5@8;=@CPF I1$a$gdb/HHp  YYY6$ & F PP0 P !$`'0*-/2p5@8;=@CPF I1$a$gdb7$ & F SP0 P !$`'0*-/2p5@8;=@CPF I1$a$gdb8$ SP0 P !$`'0*-/2p5@8;=@CPF I 1$^ a$gd[    1 !{!!!!!""?"["d"e"f"u"w""""## #-#E#F#W#Y#f#######%$&$%C%ȽۥۥߝۍȽhzh6mH sH h hH*hbh?.h9h ~h1e8hmH sH h<h6mH sH h<hmH sH h<hmHsHh h6hh[h[h[>* h?.h?.h:yhb h?.>*/ {!""f"w""~F8$ SP0 P !$`'0*-/2p5@8;=@CPF I 1$^ a$gd99$ & F VP0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gd8$ SP0 P !$`'0*-/2p5@8;=@CPF I 1$^ a$gd[ & F @ ^@ gd"F#Y##$%% &~~~E9$ & F VP0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gd & F T@ ^@ gd8$ SP0 P !$`'0*-/2p5@8;=@CPF I 1$^ a$gd[8$ SP0 P !$`'0*-/2p5@8;=@CPF I 1$^ a$gdbC%]%^%%%%%%& & & &&&&&&&&& '!'"'3'5'''''8(X(b((()|)})~)))))))**ަ޹ަޔڍ{ր{sh@ch ~>* h ~>*h ~hF>* h>* hFh1e8h:y h[h[ h ~6]hGRh?.h[>* h?.h?.hbh?. h?.>*h9h[h[h[>*h ~h1e8hhmH sH hzh6mH sH h6mH sH - &&o&&&&SSS7$ & F SP0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gd99$ VP0 @ P !$`'0*-/2p5@8;=@CPF I 1$^ a$gd99$ VP0 @ P !$`'0*-/2p5@8;=@CPF I 1$^ a$gd[&"'5'W'T9$ & F VP0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gd ~9$ VP0 @ P !$`'0*-/2p5@8;=@CPF I 1$^ a$gd[8$ SP0 P !$`'0*-/2p5@8;=@CPF I 1$^ a$gdbW'n'''''})~))I<$ & F \P0p @ P !$`'0*-/2p5@8;=@CPF I1$a$gd ~h^hgd1e89$ & F VP0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gd[7$ & F SP0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gd)*C*m**+-+v+++P:$ & F YP0p @ P !$`'0*-/2p5@8;=@CPF I1$a$gd@c9$ & F VP0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gd@c:$ & F YP0p @ P !$`'0*-/2p5@8;=@CPF I1$a$gd ~ *(*;*B*C*l*m******++,+-+C+D+U+u+v+{+|+++++,,,,,2,3,_,`,v,,,,,,=-K-L----...ֽ豩양hhy# hF>*hs3h@chF>* h ~h ~h@chFNG>*hFNGhFNGh@c>* h+I>*h@ch@c>*h@ch ~>*h ~ h@c>* h ~>*h ~h@c>*hNh@chh>*hrHh2+,3,`,,PP:$ & F YP0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gd@c:$ & F YP0p @ P !$`'0*-/2p5@8;=@CPF I1$a$gd ~9$ & F VP0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gd@c,,L--K...E///0~vnnn~~v & Fgd & FgdN & Fgds3<$ & F \P0p @ P !$`'0*-/2p5@8;=@CPF I1$a$gdF<$ \P0p @ P !$`'0*-/2p5@8;=@CPF Ih1$^ha$gd ~ ..5.6.7.G.H.e.p.s.}......./ //C/E/`/b/h/x//////00 0000000000011+1A1C1D1`1x111222222ӽӱӭӭӭӥӝhhs3\h@chs3>*h9}hsZhBRhs36 hs36hfhs35>* hy#5>*hs3hhNhKhFNG0JjhFNGUhFNGjhFNGU;00D111)2u2223@444{{{sngds3 & FgdN & Fgd & Fgds3:$ & F YP0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gd9}9$ & F VP0 @ P !$`'0*-/2p5@8;=@CPF I1$a$gdsZ 222]3d3x33@4Y444 55n5s5{55555)6I6J66888889=:?:@:A:P:Q:R:S:Z:\:e:q:r:ߣvkvh GhGR5>*\h Gh(5>*\h Ghnu5>*\ hjU>* h(5\hs3hw5>*\hs3h(5>*\hzhAD5>*hhhAD5>*h@chPXhAD5>* hNhADhRVhAD6hAD hAD5>* hs3hs3hs3hN hN6]*44455566b777777778888889=:>:?:A:Q:`gdADgds3gdADQ:R:S:w:x:y:z:::::y;z;?<@<<<==>>> ? ? ^`gd>\vgds3 ^ gdz & F @ h^hgdzgd r:v:w:x:y:z:::::::::T;;;M<s<<<<<<<<==8=~=====̼zrzjz^hzh<6mH sH hs3mH sH hNmH sH h<mH sH h<h<6mH sH h<h<mH sH h9mHsHh<h<mHsHh h H*h h 6h hNh:y>*h:yhzh<hyW;h(>* hjU>*h Gh(h Gh(5>*\h Ghnu5>*\!====>>9>=>Z>~>>> ? ? ? ?#?$?2?i??????#@u@@@@@@@@A8AGANAOAwAAºʲҦʛʐ҄҄|tʛtʐhh>\vh>\v6mH sH h`RHmH sH hRmH sH hzhz6mH sH hNhNmH sH hN6]mH sH h Ghz>*mH sH h:ymH sH h9}mH sH h>\vmH sH hNmH sH hzmH sH h+YmH sH h<mH sH hzh<6mH sH h+Y6mH sH ( ?#?$???@@@@@@@NAOAAAjBkBlB|B}BBBiC^gdKy^gd>\v^gd`RH^gdzgdz & FgdzAAA B?BjBlB|B}BBBBBBB(C\C^CjCCCCCCMDODPDQDĹĮĦzncQn#jh<6hRUmH sH hRhRmH sH jhRUmH sH hMhR6mH sH hRmH sH hohKyH*mH sH hohKy6mH sH hKymH sH h`RHh`RHmH sH h`RH6]mH sH h`RHmH sH h Ghz>*mH sH hzmH sH h>\vh>\v6mH sH h>\vh>\vH*mH sH h>\vmH sH iCjCDDEEEEEFFGG9H:HHHsItIIIJJJ^gd^gdQ{gdQ{ & Fgdzgdz^gd`RH^gdRQDDDDD E@EEEEEEE9F:FFFuFwFxFyFFFFFWGGGG̶̪̾}k^VHV}h*Th6]mH sH hmH sH hNhQ{0JmH sH #j+hNhQ{UmH sH hQ{hQ{mH sH jhQ{UmH sH hQ{hQ{6]mH sH hQ{mH sH h GhQ{>*mH sH hzmH sH hK)hK)6]mH sH hK)mH sH hRhRmH sH hRmH sH jhRUmH sH h<6hR0JmH sH GGH8H9HHHHBI]IIIIIJJJJJJJJJJKbK=L\LLL4MHM[MϹϹxjxjx\x\xh.h@6]mH sH h@h@6]mH sH h@mH sH hQ{mH sH h Gh@>*mH sH h GhQ{>*mH sH hhQ{mHsHh]h6]mH sH hmH sH h*Th*T6]mH sH h*TmH sH hGRmH sH hmH sH hh6]mH sH hhmH sH  JJJKKtLuLLLZM[MMMpNqNOO Q!QpRqRrRsRRR7S^gd.^gdQ{h^hgdQ{ & Fgd@[MMM9NWNXN\NqNNNNjOkOlOOOOOO#P+P,P8PPPPPQQQ QBQSQQQQQQQ2R4RŦŦyumufu h.h.jh.Uh.hQ{mH sH #jhNh.UmH sH h.h.mH sH h@mH sH hNh.0JmH sH #jxhNh.UmH sH jh.UmH sH hGRh.6]mH sH h.6]mH sH h.h.6]mH sH h.mH sH (4R5R6RlRmRoRpRrRsRRRRS6S7SISSSTTT TOTPTTTTTTTU~zvkcYhSfOhSfO5>*hSfO5>*\hyW;hyW;5>*\h Gh:yh+mH sH h<h+6mH sH h<h+mH sH h9mHsHh<h+mHsHh h 6h hyW;hyW;5>*\hjU5>*\hQ{mH sH  h.hQ{h.hNh.0Jjh.Uj h.U7S8SSSTTTTTUUUUV"V?V\VyVVV(WAWZWsWtWuW & FgdKgdgdyW; & Fgd+gd+UUUU8UtUvUUUUUUUUV!V4V>VQV[VnVxVVVVV W W(W8W@WPWYWZWsWuWwWWWW{phph+5>*\horhyW;5>*\h Gh9}mH sH hKmH sH h+6mH sH hzh+6mH sH h6'mH sH h+mH sH h<h+6mH sH h<h+mH sH h9mHsHh<h+mHsHh h+H*h h+6h+h(hSfOhyW;5>*'uWvWwWWWWWWJXKXXXdYeYYZZ4Z5ZZZZZ & Fgd9}^gd9}gd9} & Fgd6'^gd6'^gd`RHgd6'gdorgdWWWWWWXIXJXKXYXXX+YeYnYoYYYYYYYZZ+Z3Z4ZjZZZZZZZ[[9[][[[ߵߵߪ߃߃߃{ofo{h9}6mH sH hzh9}6mH sH h9}mH sH hKmH sH h<h6'6mH sH h<h6'mH sH h9mHsHh6'h6'mHsHhzh6'6mH sH hNh`RHmH sH h`RH6]mH sH h`RHmH sH h6'mH sH h6'h6'>*mH sH h9>*mH sH hyW;(ZZZ[[[[;\<\\\7]O]g]]]^)^*^,^<^ gdK8^8gd9} & Fgd9}^gdKgdK & FgdK & Fgd6'^gd6'^gd`RHgd6'[ \.\0\R\\\\\\\]]F]N]O]g]v]~]]]]]]^*^,^<^=^R^^^^^^^뭡|q|f|Zhoh6'6mH sH h`RHh`RHmH sH h`RH6]mH sH h`RHmH sH h6'h6'>*mH sH h9}mH sH hK6mH sH hzhK6mH sH hKmH sH h<h6'6mH sH h<h6'mH sH h9mHsHh<h6'mHsHh>\vh6'H*mH sH h6'mH sH h>\vh6'6mH sH #<^=^^^)_*_`````aabbGcHcccddddeeegd^gd G^gd6'^gd`RHgd6'^__I_q____ ````````````` aGaHaTaaaaaԪshVs#j hNh GUmH sH hQ{h GmH sH jh GUmH sH hQ{h G6]mH sH h GmH sH h6'h6'>*mH sH hGR>*mH sH h<6h6'0JmH sH #jK h<6h6'UmH sH hRh6'mH sH jh6'UmH sH hMh6'6mH sH hoh6'H*mH sH h6'mH sH aaabebbbbb%cccPdkdddeeeeeeefofJgigggAhUhhhFidieiii~i߻ߟߟߟߛ}}oooodoh G6]mH sH h.h G6]mH sH h@h G6]mH sH hq/ hGRhGR hGR>*hGRh]h G6]mH sH hh G6]mH sH hh GmH sH hQ{h GmH sH h*Th G6]mH sH h GmH sH jh GUmH sH hNh G0JmH sH %eeffggggghhhhh}i~ijj-l.l}m~mmmmmmmmmm^gd Ggdq/~iijjwjxjyjjjj0k8k9kEkkkkk)l*l,l-llllll m?mAmBmCmymzm|m}m~mmmmm޿޿Ꞗ{wlhhq/h+Ihq/5>*\hGRhNh G0Jjoh GU h.h Gjh GUh G#jhNh GUmH sH h.h GmH sH hNh G0JmH sH #jhNh GUmH sH jh GUmH sH h GmH sH hGRh G6]mH sH (mmmmmmmmmmnnYnfnhninjn~nnnnnnnnnnnn'o/o1oiorotouovowooooooooooop'p:p;p*mH sH hSfO>*mH sH hhmH sH  h5\hv&| h+5\h hThThTh`RHhy#hSfO hT5\ h25\h2h25\hh>* hy#>*7mmmmninjnnnn o2ovowoooo 0^`0gd+ `^``gdjU 0^`0gdjU 0^`0gdy# 0^`0gd `^``gdyv`gdy#`gd`RH`gdgdop*mH sH  ppp`gdjU,1h/ =!"#$% DyK tenhaveh@duq.eduyK Hmailto:tenhaveh@duq.eduyX;H,]ą'cDyK tenhaveh@duq.eduyK Hmailto:tenhaveh@duq.eduyX;H,]ą'cmDyK http://www.nuffieldbioethics.org/sites/default/files/The%20ethics%20of%20research%20involving%20animals%20-%20full%20report.pdfyK http://www.nuffieldbioethics.org/sites/default/files/The ethics of research involving animals - full report.pdfyX;H,]ą'cMDyK 0http://www.nap.edu/openbook.php?record_id=18998yK xhttp://www.nap.edu/openbook.php?record_id=18998yX;H,]ą'cDyK chttp://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm351261.pdfyK http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm351261.pdfyX;H,]ą'cQDyK qhttp://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004075.pdfyK http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004075.pdfyX;H,]ą'ciDyK 7http://www.who.int/bulletin/volumes/89/3/10-085712/en/yK http://www.who.int/bulletin/volumes/89/3/10-085712/en/yX;H,]ą'cmDyK http://www.nuffieldbioethics.org/sites/default/files/The%20ethics%20of%20research%20involving%20animals%20-%20full%20report.pdfyK http://www.nuffieldbioethics.org/sites/default/files/The ethics of research involving animals - full report.pdfyX;H,]ą'cMDyK 0http://www.nap.edu/openbook.php?record_id=18998yK xhttp://www.nap.edu/openbook.php?record_id=18998yX;H,]ą'cDyK chttp://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm351261.pdfyK http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm351261.pdfyX;H,]ą'cQDyK qhttp://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004075.pdfyK http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004075.pdfyX;H,]ą'ciDyK 7http://www.who.int/bulletin/volumes/89/3/10-085712/en/yK http://www.who.int/bulletin/volumes/89/3/10-085712/en/yX;H,]ą'c@@@ NormalCJ_HaJmH sH tH b@b *T Heading 1 x@&'5B*CJ!KH$\aJ!mHphsHtHDA@D Default Paragraph FontRiR  Table Normal4 l4a (k(No List 6U@6  Hyperlink >*B*ph4@4 LZHeader  !.)@. LZ Page Number.X@!. 6Emphasis6]N^@2N k[ Normal (Web)dd[$\$ mHsHtH<OB< *Ttitle1CJaJmHsHtH:OR: *Tdesc2CJaJmHsHtH@Ob@ *Tdetails1CJaJmHsHtH Oq *Tjrnlh45opqrstuvwxyz{|}3bL    Z f GHI\]oh]FoL/HHp {fwFY o"5Wn}!~!!"C"m""#-#v###$3$`$$$L%%K&&&E'''((D))))*u***+@,,,,,---..b////////0000001=2>2?2A2Q2R2S2w2x2y2z22222y3z3?4@44455666 7 7#7$7778888888N9O999j:k:l:|:}:::i;j;<<=====>>??9@:@@@sAtAAABBBBBCCtDuDDDZE[EEEpFqFGG I!IpJqJrJsJJJ7K8KKKLLLLLMMMMN"N?N\NyNNN(OAOZOsOtOuOvOwOOOOOOJPKPPPdQeQQRR4R5RRRRRRRSSSS;T2?2A2Q2R2S2w2y2z22222y3z3?4@44455666 7 7#7$7778888888N9O999j:k:l:|:}:::i;j;<<=====?AB[EEEpFqFGG I!IpJMMNsOOOPPdQRSTT,V@CHKPSUXY[]^`acegijlmp\]o/ " &&W')+,04Q: ?iCJ7SuWZ<^emopp:<?ABDEFGIJLMNOQRTVWZ\_bdfhknoqp;&6&G&;P<<9>x>>FkGG+HHII5JlJWXXGYYYbxbb8cc)ddBeyehXXXXXXXXXXXX  '!!8@0(  B S  ?y[ z[, {[|[ }[, ~[,[, [l [l[ [[l ['[4'[4(['[t'[n [ w[@[@[A[TA[A[A[B[TB[B[B[C[TC[C[C[D[TD[D[D[E[TE[E[E[F[TF[F[F[G[TG[G[G[H[1[T1[1[ԯ1[1[T1[1[԰1[1[T1[1[Ա1[1[T1[1[Բ1[1[T1[1[Գ1[1[T1[1”[Դ1Ô[1Ĕ[T1Ŕ[1Ɣ[Ե1ǔ[1Ȕ[T1ɔ[1ʔ[c1˔[Tc1̔[c1͔[c1Δ[d1ϔ[Td1Д[d1є[d1Ҕ[e1Ӕ[Te1Ԕ[e1Ք[e1֔[f1ה[Tf1ؔ[f1ٔ[f1ڔ[g1۔[Tg1ܔ[g1ݔ[g1ޔ[h1ߔ[Th1[h1[h1[i1[Ti1[i1[i1[j1[Tj1[j1[=[,>[l>[>[>[,?[l?[?[?[,@[l@[@[@[,A[lA[A[A[,B[lB[B[B[,C[lC[C[C[,D[lD[D[D[,E[lE[|3 [3 [3 [<4 [|4 [4[4[<5[|5[5[5[<6[|6[6[6[<7[|7[7[7[<8[|8[8[8[<9 [|9![9"[9#[<:$[|:%[:&[:'[(([D()[(*[(+[),[D)-[).[)/[*0[D*1[*2[*3[+4[D+5[+6[+7[,8[D,9[,:[,;[-<[D-=[->[-?[.@[D.A[.B[.C[/D[D/E[/F[/G[0H[D0I[0J[0K[1L[D1M[1N[1O[2P[D2Q[2R[2S[3T[D3U[3V[3W[4X[D4Y[4Z[4[[5 :COOXOOXddw/<ccOO'.@GGee++ / /)/0001H2H2c3c33334'4'444444)5050555k7r77777788v8888D9D999A:K:K:R::::::*;5;9;9;;;D=D=M====>>'>s?s?~?+@+@AdCdCrC=DDmI!K!KKKKKKK$L$LQLXLjLqLqL]M]MiMMMMMMMMOO!P(P:P:PPPPPP,Q6QVQVQQQQQQQQRRSSTTTTTTTTUU U'U'UUUVVVVVVVVVsWsWXXX*Y*Y5YZZZ9[9[\q^q^^J__zdh      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`bacedfghijklmnpoqrstuvwyxz{|}~ BJW^^Wbbu:BkkWW-8FOOpp33(/0/0/0001P2P2k3k33334/4/444444/58585 6 6q7|777778 8 88888F9F999I:Q:\:\::::::3;7;B;B;;;L=S=S====&>)>)>}???1@1@AnCyCyCHDDsI)K)KKKKKKK*L*LWLbLpLyLyLgMkMkMMMMMMMMOO'P2PBPBPPPPPP5Q@Q\Q\QQQQQQQQRRSSTTTTTTTT UU&U/U/UVVVVVVVVVWWyWyWXXX4Y7Y7YZZZ?[?[\{^^^U__dh   !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`bacedfghijklmnpoqrstuvwyxz{|}~:*urn:schemas-microsoft-com:office:smarttagsStreet;*urn:schemas-microsoft-com:office:smarttagsaddressB*urn:schemas-microsoft-com:office:smarttagscountry-region9*urn:schemas-microsoft-com:office:smarttagsplace8*urn:schemas-microsoft-com:office:smarttagsCity=*urn:schemas-microsoft-com:office:smarttags PlaceType=*urn:schemas-microsoft-com:office:smarttags PlaceName9*urn:schemas-microsoft-com:office:smarttagsState d:B{ /(/004444558!88899::::<<= =M=S=????????:@C@tAzAAABBCCCCCCCCuDyD[E`EFF!I&I'I.I3I6I7I@IIIKL LLMMMMNNPPeQnQpQQ[RaRS"S>>?@FGIIIIK6KcKKKKKLQLL:MMMMMNO&OP PPPP+Q,QcQeQQQQRR_SSS TT:TpTTTTU6UUVMVOVqVVVV YY [&[abddddhhhhhhhhhhhhhh33333333333333333333333333333333333333333333333333333333333333333  Z f ]noXp F_f"i""C"m"""v#~#$ $$$>%L%@,Z,/001S2w2z2256 7$7v8888A:{::;B====Y???8@BAsABBdCC=DsDDD4EZEEE9FpFsJJK7KQLLLLNN(OtOQQQ4RRR_SSU6U7U~UV*VVVXX]]q^^eeZfffff g'g2gjgggggh0hQhhhhhhhhhhhhhhhhhhhhhhhhhhhhhl0Goza")}W (v&PaMR7992ʀQ/=tFL# _<3`-eXn;8AN8<<= 2S=Z RI[6IOL>{fM2ObJGBWQs$ZhTAnBewZkփ2svu|9x^4zx ^`o(. ^`hH. pLp^p`LhH. @ @ ^@ `hH. ^`hH. L^`LhH. ^`hH. ^`hH. PLP^P`LhH.^`o()^`>*o(.$ $ ^$ `OJPJQJ^Jo(@ @ ^@ `o(. ^`hH. L^`LhH. ^`hH. ^`hH. PLP^P`LhH.^`o(.   ^ `hH.  L ^ `LhH. xx^x`hH. HH^H`hH. L^`LhH. ^`hH. ^`hH. L^`LhH.88^8`o(.^`o(.  L ^ `LhH.   ^ `hH. xx^x`hH. HLH^H`LhH. ^`hH. ^`hH. L^`LhH.^`o(.   ^ `hH.  L ^ `LhH. xx^x`hH. HH^H`hH. L^`LhH. ^`hH. ^`hH. L^`LhH.^`^Jo()^`^J.pLp^p`L^J.@ @ ^@ `^J.^`^J.L^`L^J.^`^J.^`^J.PLP^P`L^J.^`o(.^`OJPJQJ^Jo(- pLp^p`LhH. @ @ ^@ `hH. ^`hH. L^`LhH. ^`hH. ^`hH. PLP^P`LhH.^`o(.   ^ `hH.  L ^ `LhH. xx^x`hH. HH^H`hH. L^`LhH. ^`hH. ^`hH. L^`LhH.^`o(. ^`hH. pLp^p`LhH. @ @ ^@ `hH. ^`hH. L^`LhH. ^`hH. ^`hH. PLP^P`LhH.^`o(.   ^ `hH.  L ^ `LhH. xx^x`hH. HH^H`hH. L^`LhH. ^`hH. ^`hH. L^`LhH.^`o(. ^`hH. pLp^p`LhH. @ @ ^@ `hH. ^`hH. L^`LhH. ^`hH. ^`hH. PLP^P`LhH.^`o(.   ^ `hH.  L ^ `LhH. xx^x`hH. HH^H`hH. L^`LhH. ^`hH. ^`hH. L^`LhH.h^`OJQJo(hHh ^ `OJQJo(hHoh ^ `OJQJo(hHhx^x`OJQJo(hHhH^H`OJQJo(hHoh^`OJQJo(hHh^`OJQJo(hHh^`OJQJo(hHoh^`OJQJo(hH88^8`o(. ^`hH.  L ^ `LhH.   ^ `hH. xx^x`hH. HLH^H`LhH. ^`hH. ^`hH. L^`LhH.^`o(. ^`hH. 0 ^ `0o(. @ @ ^@ `hH. ^`hH. L^`LhH. ^`hH. ^`hH. PLP^P`LhH.^`o()^`o(. pLp^p`LhH. @ @ ^@ `hH. ^`hH. L^`LhH. ^`hH. ^`hH. PLP^P`LhH.88^8`o(. ^`hH.  L ^ `LhH.   ^ `hH. xx^x`hH. HLH^H`LhH. ^`hH. ^`hH. L^`LhH.^`o(.   ^ `hH.  L ^ `LhH. xx^x`hH. HH^H`hH. L^`LhH. ^`hH. ^`hH. L^`LhH. @ ^@ `OJQJo( ^`OJQJo(o ^`OJQJo( ^`OJQJo( ^`OJQJo(o P^P`OJQJo(  ^ `OJQJo( ^`OJQJo(o !^!`OJQJo(88^8`o(. ^`hH.  L ^ `LhH.   ^ `hH. xx^x`hH. HLH^H`LhH. ^`hH. ^`hH. L^`LhH.^`o(.   ^ `hH.  L ^ `LhH. xx^x`hH. HH^H`hH. L^`LhH. ^`hH. ^`hH. L^`LhH.^`o(.   ^ `hH.  L ^ `LhH. xx^x`hH. HH^H`hH. L^`LhH. ^`hH. ^`hH. L^`LhH.88^8`o(.^`o(.  L ^ `LhH.   ^ `hH. xx^x`hH. HLH^H`LhH. ^`hH. ^`hH. L^`LhH.88^8`o(. ^`hH.  L ^ `LhH.   ^ `hH. xx^x`hH. HLH^H`LhH. ^`hH. ^`hH. L^`LhH.^`OJPJQJ^Jo(-^`OJQJ^Jo(hHopp^p`OJQJo(hH@ @ ^@ `OJQJo(hH^`OJQJ^Jo(hHo^`OJQJo(hH^`OJQJo(hH^`OJQJ^Jo(hHoPP^P`OJQJo(hH^`o(.   ^ `hH.  L ^ `LhH. xx^x`hH. HH^H`hH. L^`LhH. ^`hH. ^`hH. L^`LhH.^`o(.hhhhhhhh88^8`o(. ^`hH.  L ^ `LhH.   ^ `hH. xx^x`hH. HLH^H`LhH. ^`hH. ^`hH. L^`LhH.Zk|9x3`-9v&GBWQ/=OQs$Za6IAN82sAnBe}W {fMz RIl09aMOLGo<=n;8S=L#^:uRr ""q%hWqo3 8!CY.Ah:gz0 _gz0kOwa"\N@k:  b-AFW_ xhPU&'!Egl&_eA(M5TUb-~a- D.~95-v1l&qo3(vF4~95~95-v1 xh_eAq%wQ2A) Z D=1 uIAt-MvF4 ""WNPU&A)RNM5TU8!CYL0~) Z:bA]A)RFW_wQ2A_~a-C bp'!Eg|4LnN@k xhTMl|4LnWpTMluRrN@k=1 uW!fu {-"wPU&kOwL0~C b~}W/[8FM6iHPd@fo|G 'X vd % < "m Mu rb 1[ ~#hlq\>'?g?97@EATBSC@gDEFEF GFNGoG`RHrH}IN>IdEIuIZ!J"L4LBLO/MNnpN$tN OseOSfO.PqNP@QGRHRSR*T, UjU'2V5iW/vW8XpHX+Y=YZ>KZsZtZ@([-[k[|]']@_$_=_i`@)a>_aaBb]b+f\vyv:yCyty~yzUYzh{Q{N{Q{z{v&|N|L }9}Y ~~;~J2h-!qCJ9Wp;JOclBF\(FZz5WuH5POdq>J#DJ 7vD<6Df)qQfAo'4d6'-V12V6Ec*eGg*f} ON_4 b.@/oF-> j-4146)#!-RWGB lMwn}=dwID Y@ G%t}n$=AP\__g``}aeh@~hp@UnknownG:Ax Times New Roman5Symbol3& :Cx Arial?5 :Cx Courier New;Wingdings"1h+M3'+M3'&X5X5!4dhdh2qHX ?w2HCE-656 END OF LIFE ETHICS h_tenhave Henk ten Have|                       Oh+'0 $ D P \ ht| HCE-656 END OF LIFE ETHICS h_tenhave Normal.dotHenk ten Have2Microsoft Office Word@@͚@aZ@aZX՜.+,D՜.+,L hp  UNESCO5dh' HCE-656 END OF LIFE ETHICS Title  8@ _PID_HLINKSA H-2!7http://www.who.int/bulletin/volumes/89/3/10-085712/en/s)Qqhttp://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004075.pdfs5}chttp://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm351261.pdfs`0http://www.nap.edu/openbook.php?record_id=18998sl,phttp://www.nuffieldbioethics.org/sites/default/files/The ethics of research involving animals - full report.pdfs-27http://www.who.int/bulletin/volumes/89/3/10-085712/en/s)Qqhttp://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004075.pdfs5} chttp://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm351261.pdfs` 0http://www.nap.edu/openbook.php?record_id=18998sl,phttp://www.nuffieldbioethics.org/sites/default/files/The ethics of research involving animals - full report.pdfs)mailto:tenhaveh@duq.edus)mailto:tenhaveh@duq.edus  !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrtuvwxyz{|} Root Entry FAZ Data s1Table~*WordDocument.SummaryInformation(DocumentSummaryInformation8CompObjq  FMicrosoft Office Word Document MSWordDocWord.Document.89q