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

1. Quality System Documentation forResearch EthicsClinical Effectiveness UnitDivision, 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. Goal: To develop a sound ethical framework for clinical research HA Policy Consideration • Protect research subjects (HA patients) • Uphold standard of research conduct among employees (& affiliated investigators) • Manage research-related liabilities • Ensure service priority

4. Research Ethics in HA: Past

5. Insufficient enforcement mechanism Performance did not meet ICH-GCP standard, a prerequisite for international drug trials 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 Rely on EC secretaries to extract information from study protocols No independent oversight of REC performance

6. Research Ethics in HA: Present

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

8. Importance of Documentation System Enforceability • 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

9. Documentation sustains Enforceability

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. Practice point: Corrections made in document must be crossed out (still see through), initialled & dated 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

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

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

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

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

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

20. 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 • Handlecomplaint & 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 responsibilityin technical, administrative & fiscal management of study

22. Document Internalization within Organization

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