1. HA Research Ethics Development HA REC Meeting 6/2/2004 HA REC Meeting 6/2/2004

2. Revamp Exercise 2002-2003 Approved by MSDC (57 th meeting, MSDC-P140, Dec 17, 2001) A cluster-based REC approach, with a central mechanism for establishing standards & harmonizing development Approved by MSDC (57 th meeting, MSDC-P140, Dec 17, 2001) A cluster-based REC approach, with a central mechanism for establishing standards & harmonizing development

3. Progress

4. Progress - HA REC with new TOR, Jun 2002 Harmonize clinical research ethics in HA hospitals through standards setting Coordinate training for REC members Supervise a central registry of clinical trials involving HA patients Supervise audit for clinical research ethics related performance in HA Monitor and disseminate global developments in clinical research ethics Handle appeal against Cluster REC decision Harmonize clinical research ethics in HA hospitals through standards setting Coordinate training for REC members Supervise a central registry of clinical trials involving HA patients Supervise audit for clinical research ethics related performance in HA Monitor and disseminate global developments in clinical research ethics Handle appeal against Cluster REC decision

5. Progress – Establishing Standards & Operation Procedures by a Quality System approach HA Guide for Cluster REC Developed & approved by HA REC (Feb 2003): Minimal standards, framework for SOP & Form development ICH GCP (E6) Other references, e.g. FDA IRB Guide International requirements & practices International requirements & practices HA policy, AP target, Section III Standards Standard Operating Procedure & Forms Developed & approved by Cluster REC (2-4Q 2003): Guide REC operation Local requirements & practices Declaration of Helsinki

6. Progress - RE web-page launched Mar 2002

7. Progress - Commission Training (REC) Cluster REC No. participated HKW-HKU33 HKE31 KC&KE29 KW33 NTE-CU11 NTW9 HAHO & Universities 8 Total154 A 12-hr course by CTC, HKU & CEU Organized 3 courses during 1-4Q 2003 A 12-hr course by CTC, HKU & CEU Organized 3 courses during 1-4Q 2003

8. Progress – Central Registry 1. Application ref number 12. Is the test drug licensed in HK? 2. REC name 13. Investigational invasive procedure 3. Study title 14. Is there an Independent Data Monitoring Committee? 4. Name of PI 15. REC review decision 5. Affiliated institute of PI 16. Protocol submission date 6. Study sites (local) 17. REC decision date 7. Is this an international study 18. Proposed study start date 8. Study design 19. Intended completion date 9. No. of local participants planned 20. Source of funding 10. Investigational product 21. Pre-mature termination of study (date & reason) 11. Phase of drug trial 22. Final report receipt date In progress Minimal dataset In progress Minimal dataset

9. ClusterEstablishChairman Secretary (FT equivalent) No. of Members No. of panels SOP & Forms HKW-HKU Mar 2003 Prof C L Lai 2616yes HKE Sept 2003 Dr MA Hok Cheung 0.3376yes KC&KE Sept 2003 Dr LEE Kin Hung 0.4293yes KW Sept 2003 Dr Lawrence C H TANG 1344yes NTE-CU Nov 2002 Prof Jean Woo 2.4152yes NTW Feb 2003 Dr Albert C Y LO 0.7151yes Progress – Cluster REC 29 hospital-based RECs  6 cluster-based RECs & merging with the respective medical faculty IRB

10. Cluster Meeting Frequency Applications received Meetings held Approved Expedited review HKW-HKUBi-weekly74320725 658 (91%) HKE On demand 23116 16 (100%) KC&KEMonthly65455 46 (84%) KWMonthly102492 53 (58%) NTEMonthly60914492 41 (8%) NTW 1-2 monthly 59840 12 (30%) Cluster REC Operation (From establishment to Dec 2003)

11. Major Concerns

12. Liability of REC Member Chapter 113: HA Ordinance. Section 23: Protection of members of Authority, etc.. Subsection 1. No member of the Authority or of any committee, acting in good faith, shall be personally liable for any act done or default made (a) by or on behalf of the Authority; or (b) by or on behalf of any committee, in the performance or purported performance of the functions, or the exercise or purported exercise of the powers, imposed or conferred on the Authority under this Ordinance. Chapter 113: HA Ordinance. Section 23: Protection of members of Authority, etc.. Subsection 1. No member of the Authority or of any committee, acting in good faith, shall be personally liable for any act done or default made (a) by or on behalf of the Authority; or (b) by or on behalf of any committee, in the performance or purported performance of the functions, or the exercise or purported exercise of the powers, imposed or conferred on the Authority under this Ordinance.

13. Mx of Research-related Liability Liability cannot be waived Indemnity/insurance is a mean to transfer/finance risk Indemnity by a sponsor is conditional Need to manage liability proactively –Ethical research conduct (code of practice & training for investigator) –Administrative approval –Ethical review & study monitoring –SOP for study site, study site inspection –REC performance monitoring Liability cannot be waived Indemnity/insurance is a mean to transfer/finance risk Indemnity by a sponsor is conditional Need to manage liability proactively –Ethical research conduct (code of practice & training for investigator) –Administrative approval –Ethical review & study monitoring –SOP for study site, study site inspection –REC performance monitoring

14. Indemnity & Insurance Indemnity by Sponsor usually excludes malpractice, negligence, error, omission, or protocol violation, etc. Indemnity should cover both the institute & all investigators An insurance backed indemnity is most desirable It is desirable for a research institute to acquire insurance for malpractice, negligence & when itself acts as a sponsor Indemnity should cover both the institute & all investigators An insurance backed indemnity is most desirable It is desirable for a research institute to acquire insurance for malpractice, negligence & when itself acts as a sponsor Insurance company Sponsor Institute Investigators Indemnifier Indemnitee Indemnifier Indemnitee Research subjects (Consent)

15. “HA med mal” will provide indemnity against claims in connection with Clinical Trial provided that there is negligence, error or omission on the part of HA (or other Insured party as defined)

16. Multi-center Trials The authority of each REC over study sites is defined, following the hospital cluster arrangement HA REC endorsed overriding arrangements for cross cluster approval necessary in multi-centre trials (see section 3.3b, HA Guide for Cluster REC): i.One review by a lead REC ii.Separate reviews by Cluster RECs iii.Expedited review basing on documents of other Cluster RECs The authority of each REC over study sites is defined, following the hospital cluster arrangement HA REC endorsed overriding arrangements for cross cluster approval necessary in multi-centre trials (see section 3.3b, HA Guide for Cluster REC): i.One review by a lead REC ii.Separate reviews by Cluster RECs iii.Expedited review basing on documents of other Cluster RECs

17. Cluster REC maintains autonomy

18. The Way Forward Approved by MSDC (72 nd meeting, MSDC-P181, 15/12/2003) Develop – Code of Practice for investigator – SOP for study site – Central Register (involving HA patients) HA should develop its R&D capability by collaborating relevant resources, e.g. the KPO team More training opportunities on research related matters Monitor/audit Cluster REC performance Approved by MSDC (72 nd meeting, MSDC-P181, 15/12/2003) Develop – Code of Practice for investigator – SOP for study site – Central Register (involving HA patients) HA should develop its R&D capability by collaborating relevant resources, e.g. the KPO team More training opportunities on research related matters Monitor/audit Cluster REC performance