1. Quality System Documentation for Research Ethics Clinical Effectiveness Unit Division, PS & MD 2005

2. BACKGROUND HK has no Statute specifically on clinical research Ethical oversight relies on – Professional self-discipline – Administrative control of academia & healthcare providers

3. HA Policy Consideration Protect research subjects (HA patients) Uphold standard of research conduct among employees (& affiliated investigators) Manage research-related liabilities Ensure service priority Goal: To develop a sound ethical framework for clinical research

4. Research Ethics in HA: Past InfrastructureProgress 1992- 1994 1 Ethics Committee at HAHO replaced HSD/DH’s EC University’s IRB/EC (teaching hospitals) Inherited existing practice Mandatory ethical review Compliance with applicable regulatory requirements & Declaration of Helsinki 1995- 2001 Set up hospital-based ECs (up to 42 at year 2001) Expanded review capacity to cope with increasing research activities

5. A Survey at 2001 29 Hospital Ethics Committees – – < half had operating guideline – – only 2 regularly met to vet application – – < 1/3 vet indemnity document – – No standard requirement on application dossier – ely on EC secretaries to extract information from study protocols – Rely on EC secretaries to extract information from study protocols – No independent oversight of REC performance Insufficient enforcement mechanism Performance did not meet ICH-GCP standard, a prerequisite for international drug trials

6. Research Ethics in HA: Present InfrastructureProgress 2002- 2-tier structure - HA REC (standard setting, compliance oversight, appeal) - HA REC (standard setting, compliance oversight, appeal) - Consolidated 42 Hosp ECs to 6 Cluster RECs (ethical review, study oversight) - Consolidated 42 Hosp ECs to 6 Cluster RECs (ethical review, study oversight) - HA & CU, HKU merged their respective RECs in 2002 - HA & CU, HKU merged their respective RECs in 2002 Segregate standard setting function (HA REC) from execution (Cluster REC) Assure outcome by a Quality System approach using explicit standards & procedures to - enforce ethical principles - enforce ethical principles - harmonize practices (HA & medical schools) - harmonize practices (HA & medical schools) - meet global development - meet global development - enable compliance oversight - enable compliance oversight

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

8. Importance of Documentation System Internalize ethical principles & global best practices into explicit “HA standards” Provide clear expectations on performance Align system & process to policy Assure consistent, impartial & transparent processes Delineate ethical responsibilities Facilitate communication, feedback, training & compliance oversight Enforceability

9. Documentation sustains Enforceability Document generation Engage (empower) operators to review current practice & system Internalize knowledge & accepted practices into institution rules Validation Ensure alignment to policy & achievability Approval Assign authority (& necessary system support) Standardized record forms Provide audit trails on control critical events Dissemination, training Inform & equip relevant personnel Document control Ensure right (update) information Document maintenance Ensure continual suitability

10. Importance of Documentation System Internalize ethical principles & global best practices into explicit “HA standards” Provide clear expectations on performance Align system & process to policy Assure consistent, impartial & transparent processes Delineate ethical responsibilities Facilitate communication, feedback, training & compliance oversight Procedural justice

11. Documentation promotes Procedural Justice Consistent, impartial & transparent procedures are the best guarantee for fair outcomes & to gain trust Justice must be seen to be done Standard of documentation must allow evaluation of the conduct of review & the quality of the decision reached – In audit, not documented ≡ not done – In dispute, intention is judged (inferred) objectively 必須有目共睹 Practice point: Corrections made in document must be crossed out (still see through), initialled & dated

12. Importance of Documentation System Internalize ethical principles & global best practices into explicit “HA standards” Provide clear expectations on performance Align system & process to policy Assure consistent, impartial & transparent processes Delineate ethical responsibilities Facilitate communication, feedback, training & compliance oversight Sharing ethical responsibilities

13. CUHK, HKU Medical Faculty Hospital Authority Study Site Administration Teaching hospitalsNon-teaching hospitals Sharing Ethical Responsibilities Sponsors Cluster REC Investigators Research subjects Policy & Standards Compliance oversight Training Appeal (REC decision) Dept of HealthMedical Council Global references University facilities Research Organizations Research Organizations HA patients Non-HA patients Research subjects Investigators HA REC Investigator privilege Study site facilities Clinical trial agreement Indemnity agreement Risk Mx, insurance Handle complaints & malpractice Policy & requirements on research Study Site Administration CU / HKU REC Gate keeping Ethical review Study oversight AE oversight Progress reports HA’s HA’s jurisdiction jurisdiction IDMC Site audit

14. Importance of Documentation System Internalize ethical principles & global best practices into explicit “HA standards” Provide clear expectations on performance Align system & process to policy Assure consistent, impartial & transparent processes Delineate ethical responsibilities Facilitate communication, feedback, training & compliance oversight Compliance oversight & CQI

15. Documentation enables Compliance Oversight REC’s performance is subject to monitoring Annual inspection – Review REC operating procedures against HA standards & requirements – Random checking of records for compliance to HA standards & REC operating procedures – Interview staff on practices Continuous improvement: corrective actions, revising standards, refresher training

16. by adopting a Quality System approach HA delivers research ethics through Research Subject Protection Investigators Hospital (Study Sites ) Administration HA REC Cluster RECs

17. Corresponding to the parties involved, there are 3 Guiding Documents & a number of forms

18. Documents accommodate Different Obligations & Audience Perspectives e.g. on handling SAE 1.Ensure investigator competence 2.Administrative oversight & legal support 1.Study oversight requires prompt SAE reporting to REC 2.Review all SAE reports 3.Alert HA REC if SAE demands study termination REC / IRB Study Sites 1. Study has measure for early detection & Mx of possible adverse outcome Investigators 2. Inform participants affected (& their clinicians if indicated) & report to sponsors, REC, HA Legal Services & Regulatory Agency (if required by law) 3. Update participants (& consent form) if the SAE is relevant to subjects’ willingness to participate

19. 1. REC Guide (internalizing best practices) HA Guide for Cluster REC Established by HA REC: HA-wide StandardsHA-wide Standards Guiding document for Cluster RECGuiding document for Cluster REC Enables auditEnables audit Basis for harmonizing with CU & HKUBasis for harmonizing with CU & HKU ICH GCP (E6) Other references, e.g. FDA IRB Guide Internationalrequirements & practices Applicable regulations Professional Code & Conduct HA policy Cluster REC Standard Operating Procedure & Forms Established by Cluster REC: Guides operationGuides operation Enables auditEnables audit Local standards & practices Declaration of Helsinki Local requirements

20. 2. Study Site Guide 2. Study Site Guide Institutes engaging in clinical research are obliged to: – Support REC – Control research privilege: investigator qualification, policy in granting access right to non-employees – Verify adequate facility & resource support for study & no undue influence on service – Undertake formal dealings with sponsor: indemnity agreement, clinical trial agreement – Manage risk: insurance, policy on collaboration with non-affiliated study sites – Handle complaint & misconduct

21. 3. Investigator’s Code of Practice Has prime responsibility in protecting research subjects & be answerable to the institution. Investigator should: – qualify scientifically, i.e. proficient in the area of study – understand & willing to comply with regulatory, professional & institutional requirements on research – declare conflict of interest – abide by REC decisions PI has overall responsibility in technical, administrative & fiscal management of study

22. Document Internalization within Organization HA levelCluster LevelHospital level REC Guide ++ – Investigator’s COP + –– Study Site Guide +±±

23. QS documentation is especially important for:  Large organization  Activities characterized by ― high stake (narrow safety margin, serious consequences) ― multi-parties involvement ― labor intensive processes