Quality System Documentation Quality System Documentation

forfor

Research EthicsResearch Ethics

Clinical Effectiveness UnitClinical Effectiveness Unit

Division, PS & MD Division, PS & MD

20052005

BACKGROUNDHK has no Statute specifically on clinical researchEthical oversight relies on– Professional self-discipline– Administrative control of academia &

healthcare providers

HA Policy ConsiderationHA Policy Consideration

Protect research subjects (HA patients)Protect research subjects (HA patients)

Uphold standard of research conduct among Uphold standard of research conduct among employees (& affiliated investigators)employees (& affiliated investigators)

Manage research-related liabilitiesManage research-related liabilities

Ensure service priorityEnsure service priority

Goal: To develop a sound ethical framework for clinical research

Research Ethics in HA: PastResearch Ethics in HA: PastInfrastructureInfrastructure ProgressProgress

1992-1992-19941994

1 Ethics Committee 1 Ethics Committee at HAHO replaced at HAHO replaced HSD/DH’s ECHSD/DH’s EC

University’s IRB/EC University’s IRB/EC (teaching hospitals)(teaching hospitals)

Inherited existing practiceInherited existing practice

Mandatory ethical reviewMandatory ethical review

Compliance with applicable Compliance with applicable regulatory requirements &regulatory requirements & Declaration of HelsinkiDeclaration of Helsinki

1995- 1995- 20012001

Set up hospital-based Set up hospital-based ECs (up to 42 at year ECs (up to 42 at year 2001)2001)

Expanded review capacity Expanded review capacity to cope with increasing to cope with increasing research activitiesresearch activities

A Survey at 2001A 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 ely on EC secretaries to extract information

from study protocolsfrom study protocols– No independent oversight of REC performanceNo independent oversight of REC performance

Insufficient enforcement mechanism Performance did not meet ICH-GCP standard,

a prerequisite for international drug trials

Research Ethics in HA: PresentResearch Ethics in HA: PresentInfrastructureInfrastructure ProgressProgress

2002-2002- 2-tier structure2-tier structure - HA REC (standard - HA REC (standard

setting, compliance setting, compliance oversight, appeal)oversight, appeal)

- Consolidated 42 Hosp - Consolidated 42 Hosp ECs to 6 Cluster RECs ECs to 6 Cluster RECs (ethical review, study (ethical review, study oversight)oversight)

- HA & CU, HKU - HA & CU, HKU merged their merged their respective RECs in respective RECs in 20022002

Segregate standard setting Segregate standard setting function function (HA REC)(HA REC) from from execution execution (Cluster REC)(Cluster REC)Assure outcome by a Quality Assure outcome by a Quality System approach using System approach using explicit explicit standards & procedures standards & procedures toto

- enforce ethical principles - enforce ethical principles - harmonize practices (HA & - harmonize practices (HA &

medical schools)medical schools) - meet global development- meet global development - enable compliance oversight- enable compliance oversight

Quality System Documentation

as the backbone of Research Ethics

practice (& development) in HA

Importance of Documentation SystemImportance of Documentation System

Internalize ethical principles & global best practices Internalize ethical principles & global best practices into explicit “HA standards”into explicit “HA standards”

Provide clear expectations on performanceProvide clear expectations on performance

Align system & process to policyAlign system & process to policy

Assure consistent, impartial & transparent processesAssure consistent, impartial & transparent processes

Delineate ethical responsibilitiesDelineate ethical responsibilities

Facilitate communication, feedback, training & Facilitate communication, feedback, training & compliance oversightcompliance oversight

EnforceabilityEnforceability

Documentation sustains EnforceabilityDocumentation sustains EnforceabilityDocument Document generationgeneration

Engage (empower) operators to review current Engage (empower) operators to review current practice & systempractice & systemInternalize knowledge & accepted practices Internalize knowledge & accepted practices into institution rulesinto institution rules

ValidationValidation Ensure alignment to policy & achievabilityEnsure alignment to policy & achievabilityApprovalApproval Assign authority (& necessary system support)Assign authority (& necessary system support)Standardized Standardized record formsrecord forms

Provide audit trails on control critical eventsProvide audit trails on control critical events

Dissemination, Dissemination, trainingtraining

Inform & equip relevant personnelInform & equip relevant personnel

Document Document controlcontrol

Ensure right (update) informationEnsure right (update) information

Document Document maintenancemaintenance

Ensure continual suitabilityEnsure continual suitability

Importance of Documentation SystemImportance of Documentation System

Internalize ethical principles & global best practices Internalize ethical principles & global best practices into explicit “HA standards”into explicit “HA standards”

Provide clear expectations on performanceProvide clear expectations on performance

Align system & process to policyAlign system & process to policy

Assure consistent, impartial & transparent processesAssure consistent, impartial & transparent processes

Delineate ethical responsibilitiesDelineate ethical responsibilities

Facilitate communication, feedback, training & Facilitate communication, feedback, training & compliance oversightcompliance oversight

Procedural justiceProcedural justice

Documentation promotes Procedural JusticeDocumentation promotes Procedural Justice

Consistent, impartial & transparent procedures are Consistent, impartial & transparent procedures are the best guarantee for fair outcomes & to gain trustthe best guarantee for fair outcomes & to gain trustJustice must be seen to be doneJustice must be seen to be doneStandard of documentation Standard of documentation must allow evaluation of must allow evaluation of the conduct of review & the quality of the decision the conduct of review & the quality of the decision reachedreached– In audit, In audit, not documented ≡ not donenot documented ≡ not done– In dispute, intention is judged (inferred) objectivelyIn dispute, intention is judged (inferred) objectively

必須有目共睹必須有目共睹

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

Importance of Documentation SystemImportance of Documentation System

Internalize ethical principles & global best practices Internalize ethical principles & global best practices into explicit “HA standards”into explicit “HA standards”

Provide clear expectations on performanceProvide clear expectations on performance

Align system & process to policyAlign system & process to policy

Assure consistent, impartial & transparent processesAssure consistent, impartial & transparent processes

Delineate ethical responsibilitiesDelineate ethical responsibilities

Facilitate communication, feedback, training & Facilitate communication, feedback, training & compliance oversightcompliance oversight

Sharing ethical responsibilitiesSharing ethical responsibilities

CUHK, HKUMedical Faculty

Hospital Authority

Study Site Administration

Teaching hospitalsNon-teachinghospitals

Sharing Ethical ResponsibilitiesSharing Ethical ResponsibilitiesSponsors

Cluster REC

Investigators

Research subjects

• Policy & Standards• Compliance oversight• Training• Appeal (REC decision)

Dept of Health Medical Council Global references

University facilities

Research OrganizationsResearch Organizations

HApatients

Non-HApatients

Research subjects

Investigators

HA REC

• Investigator privilege• Study site facilities• Clinical trial

agreement• Indemnity agreement• Risk Mx, insurance• Handle complaints &

malpractice

Policy & requirements on researchStudy Site

Administration

CU / HKU REC

• Gate keeping• Ethical review• Study oversight• AE oversight• Progress reports

HA’sHA’s jurisdictionjurisdiction

• IDMC• Site audit

Importance of Documentation SystemImportance of Documentation System

Internalize ethical principles & global best practices Internalize ethical principles & global best practices into explicit “HA standards”into explicit “HA standards”

Provide clear expectations on performanceProvide clear expectations on performance

Align system & process to policyAlign system & process to policy

Assure consistent, impartial & transparent processesAssure consistent, impartial & transparent processes

Delineate ethical responsibilitiesDelineate ethical responsibilities

Facilitate communication, feedback, training & Facilitate communication, feedback, training & compliance oversightcompliance oversightCompliance oversight & CQICompliance oversight & CQI

Documentation enables Compliance OversightDocumentation enables Compliance Oversight

REC’s performance is subject to monitoringREC’s performance is subject to monitoringAnnual inspectionAnnual inspection– Review REC operating procedures against HA Review REC operating procedures against HA

standards & requirementsstandards & requirements– Random checking of records for compliance to Random checking of records for compliance to

HA standards & REC operating proceduresHA standards & REC operating procedures– Interview staff on practicesInterview staff on practicesContinuous improvement: corrective actions, Continuous improvement: corrective actions, revising standards, refresher trainingrevising standards, refresher training

by adopting a Quality System approachby adopting a Quality System approach

HA delivers research ethics throughHA delivers research ethics through

Research Research SubjectSubjectProtectionProtection

InvestigatorsInvestigators

HospitalHospital(Study Sites(Study Sites))

AdministrationAdministration

HA RECHA RECCluster RECsCluster RECs

Corresponding to the Corresponding to the parties involved, there are parties involved, there are

3 Guiding Documents3 Guiding Documents

& a number of forms& a number of forms

Documents accommodate Different Documents accommodate Different Obligations & Audience PerspectivesObligations & Audience Perspectives

e.g. on e.g. on handling handling SAESAE

1. Ensure investigator competence2. Administrative oversight & legal

support

1. Study oversight requires prompt SAE reporting to REC

2. Review all SAE reports3. Alert HA REC if SAE demands

study termination

REC / IRBREC / IRB

Study SitesStudy Sites

1. Study has measure for early detection& Mx of possible adverse outcome

InvestigatorsInvestigators

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

1. 1. REC Guide (internalizing best practices)REC Guide (internalizing best practices)

HA Guide forCluster REC

Established by HA REC:Established by HA REC:• HA-wide StandardsHA-wide Standards• Guiding document for Cluster Guiding document for Cluster

RECREC• Enables auditEnables audit• Basis for harmonizing with CU Basis for harmonizing with CU

& HKU& HKU

ICH GCP (E6)Other references,e.g. FDA IRB Guide

InternationalInternationalrequirementsrequirements& practices& practices

Applicable regulationsProfessional Code & Conduct

HA policy

Cluster REC Standard OperatingProcedure & Forms

Established by Cluster REC:Established by Cluster REC:• Guides operationGuides operation• Enables auditEnables audit

Local standards & practicesLocal standards & practices

Declaration of Helsinki

Local requirementsLocal requirements

2. Study Site Guide2. Study Site Guide

Institutes engaging in clinical research are obliged to: Institutes engaging in clinical research are obliged to: – Support RECSupport REC– Control research privilege: investigator qualification, Control research privilege: investigator qualification, policy in gpolicy in granting access right to non-employeesranting access right to non-employees

– Verify adequate facility & resource support for study Verify adequate facility & resource support for study & no undue influence on service& no undue influence on service

– Undertake formal dealings with sponsor: indemnity Undertake formal dealings with sponsor: indemnity agreement, clinical trial agreementagreement, clinical trial agreement

– Manage risk: insurance, policy on collaboration with Manage risk: insurance, policy on collaboration with non-affiliated study sitesnon-affiliated study sites

– HandleHandle complaint complaint & misconduct& misconduct

3. Investigator’s Code of Practice3. Investigator’s Code of Practice

Has prime responsibility in protecting research subjects Has prime responsibility in protecting research subjects & be answerable to the institution. Investigator should:& be answerable to the institution. Investigator should:– qualify scientifically, i.e. proficient in the area of studyqualify scientifically, i.e. proficient in the area of study– understand & willing to comply with regulatory, understand & willing to comply with regulatory,

professional & institutional requirements on researchprofessional & institutional requirements on research– declare conflict of interest declare conflict of interest – abide by REC decisionsabide by REC decisions

PI has overall responsibilityPI has overall responsibility in in technical, administrativetechnical, administrative && fiscal management of fiscal management of studystudy

Document Internalization within OrganizationDocument Internalization within Organization

HA level Cluster Level Hospital level

REC Guide + + –

Investigator’s COP + – –

Study Site Guide + ± ±

QS documentation is especially important for:Large organizationActivities characterized by

― high stake (narrow safety margin, serious consequences)

― multi-parties involvement― labor intensive processes