1. Document Development for Research Ethics Clinical Effectiveness Unit Division, PS & MD 2005

3. BACKGROUND 1.HK has no specific Statute on clinical research 2.Rely on professional self-discipline & administrative control

4. Important Policy Considerations Protection of human research subjectsProtection of human research subjects Comply with Declaration of Helsinki, ICH-GCP, international best practices & local regulationsComply with Declaration of Helsinki, ICH-GCP, international best practices & local regulations Mandatory ethical review, approval & monitoring by a recognized REC/ IRBMandatory ethical review, approval & monitoring by a recognized REC/ IRB Management of research-related liabilitiesManagement of research-related liabilities Basic competence of investigators & facilitiesBasic competence of investigators & facilities Should not compete with service needsShould not compete with service needs

5. Development: Past & Present 1992-HA Ethics Committee replaced HSD/DH’s Ethics Committee 1995-Evolved a 2-tier mechanism Central HA Ethics Committee (on policy) Hospital Ethics Committees (on operation) ~ 40 Hospital-ECs at 2001, < half had operating guidelines, < one-third reviewed indemnity arrangement, only 2 regularly met to vet applications 2002-Consolidated hospital ECs into Cluster-RECs Merging with corresponding REC/ IRB of CU & HKU’s medical faculties HA-REC to establish standards, guidelines & harmonize research ethics development in HA

6. Reason for change Ensure HK’s participation in drug trials by complying with ICH-GCPEnsure HK’s participation in drug trials by complying with ICH-GCP Address system weaknessAddress system weakness – Variation in standards – Few REC met to vet – Documents not user-friendly & may be inadequate – Process relied heavily on REC secretaries – Insufficient support to most RECs – Lack of training To consolidate resource, expertise & harmonize practicesTo consolidate resource, expertise & harmonize practices

7. Progress Revamp HA REC2Q 02 Establish SOP & supporting forms for Cluster REC1Q 03 Consolidate hospital ECs into Cluster RECs3-4Q 02 Merging with the University REC/IRBs3-4Q 02 REC training4Q 02 - 1Q 03 Develop database Mx software for Cluster REC4Q 04 Establish a central database on Clinical Research4Q 04 Establish Study Site Guide & Investigator’s COP4Q 04 Investigator training & refreshing training on REC1Q 05 - Develop on-line submission of application3-4Q 05

8. APPROACH Quality System Documentation as backbone of Research Ethics practice (& development) in HA

9. Why ?

10. Provides Anchorage Align structure, process & output requirements to policy Align structure, process & output requirements to policy Delineate responsibility / accountability of relevant parties & personnel Delineate responsibility / accountability of relevant parties & personnel Convert knowledge & accepted practices to institution rules Convert knowledge & accepted practices to institution rules – Guide specific tasks – Describe expectation on performance (competence) – Basis for training & audit

11. In-process Metrics for CQI Documentation steps Document generation & maintenance Validation Approval Dissemination, training Design record forms Benefits Engage (empower) practitioners to (regularly) review current practice (& system) Ensure practicability (& align to policy) Assign authority (& system support) Communicate to (& equip) practitioners Control critical events (QA, provide audit trail)

12. Ensures Applicability Internalizing: convert knowledge & accepted practices into institution rules (deliberation to adapt into local context)Internalizing: convert knowledge & accepted practices into institution rules (deliberation to adapt into local context) – From generic to specific requirements – Customize with system, expertise & resources (practical consideration) – Tailor requirement to audiences’ perspectives (drafting skill for technical communication) Approval: assign authority to document Approval: assign authority to document

13. Assures Right Information To preclude use of obsolete documents, documents are To preclude use of obsolete documents, documents are – uniquely identified – filed in a readily accessible source – distributed to concerned personnel & workplaces (consider web-based technology) – Obsolete document for archive is clearly denoted Scheduled review to ensure continual validity Scheduled review to ensure continual validity

14. QS documentation is especially important for: Large organization High stake activities ― Narrow safety margin ― Involves multi-parties ― Labor intensive

15. 3 Pillars ProtectingResearch Subjects 3 Pillars Protecting Research Subjects Protection of Human Research Subjects REC / IRB Study Site Authority (hospital/ HA, University) Investigators (research team) They have related but different roles & responsibilities, thus require correspondingly different guiding documents

16. Document Should Accommodate Audience’s Perspective e.g. on handling SAE - Ensure all SAEs with potential claim & legal implication are reported to Legal Services Section of HAHO - Ensure investigator competence 1.Require PI to report SAE to REC 2.Review SAE reports 3.Notify HA REC if SAE demands study termination (Alert/Recall) REC / IRB Study Sites 1. Institute measures for early detection & Mx of possible adverse outcomes Investigators 2. Report SAE to - Participants (& their clinicians if indicated) - Sponsors & REC (in accordance with ICH-GCP) - Legal Services Section of HAHO (if there is potential claim & legal implication) - Regulatory agency (if required by law) 3. Update participants if the SAE may be relevant to their willingness to continue participate in study

17. 1. REC / IRB Guide (internalizing good practices) HA Guide for Cluster REC Established by HA REC: HA-wide StandardsHA-wide Standards Framework for SOP & Form development in clustersFramework for SOP & Form development in clusters ICH GCP (E6) Other references, e.g. FDA IRB Guide Internationalrequirements & practices Local regulation HA policy Cluster REC Standard Operating Procedure & Forms Established by Cluster REC: Guides operationGuides operation Enables auditEnables audit Local requirements & practices Declaration of Helsinki

18. 2. Investigator’s Code of Practice Investigators have the primary responsibility for protecting the rights & welfare of human research subjects. They must comply with all applicable provisions, such as – Ethical responsibility – Right of participants – Consent to research – Regulatory requirements, professional standard, institutional policies & procedures – Relationship with external sponsor – Interaction with REC & study site administration – Handling potential conflict of interest

19. 3. HA Study Site Guide All institutions involved in clinical research have a responsibility to protect research participants All institutions involved in clinical research have a responsibility to protect research participants – Explicit policy & procedures on human protection in research – Sufficient facilities & competent investigators – Formal vetting & approval procedure – Study monitoring, esp. record management, SAE handling, complaint management, procedure to deal with incompetence & misconduct – Training, risk management – Interfaces with REC & HAHO Administrative procedures may be handled differently from one institution to another

20. Level of Document Internalization HA levelCluster LevelHospital level REC/IRB Guide ++ – Investigator’s COP + –– Study Site Guide +±±