Document Development Document Development

forfor

Research EthicsResearch Ethics

Clinical Effectiveness UnitClinical Effectiveness Unit

Division, PS & MD Division, PS & MD

20052005

BACKGROUND

1. HK has no specific Statute on clinical research

2. Rely on professional self-discipline & administrative control

Important Policy ConsiderationsImportant Policy Considerations

• Protection of human research subjectsProtection of human research subjects

• Comply with Declaration of Helsinki, ICH-GCP, Comply with Declaration of Helsinki, ICH-GCP, international best practices & local regulationsinternational best practices & local regulations

• Mandatory ethical review, approval & monitoring by a Mandatory ethical review, approval & monitoring by a recognized REC/ IRBrecognized 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

Development: Past & PresentDevelopment: 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

Reason for changeReason for change

• Ensure HK’s participation in drug trials by complying Ensure HK’s participation in drug trials by complying with ICH-GCPwith ICH-GCP

• Address system weaknessAddress system weakness– Variation in standardsVariation in standards– Few REC met to vetFew REC met to vet– Documents not user-friendly & may be inadequateDocuments not user-friendly & may be inadequate– Process relied heavily on REC secretariesProcess relied heavily on REC secretaries– Insufficient support to most RECsInsufficient support to most RECs– Lack of trainingLack of training

• To consolidate resource, expertise & harmonize To consolidate resource, expertise & harmonize practicespractices

ProgressProgress

Revamp HA REC 2Q 02Establish SOP & supporting forms for Cluster REC 1Q 03Consolidate hospital ECs into Cluster RECs 3-4Q 02Merging with the University REC/IRBs 3-4Q 02REC training 4Q 02 - 1Q 03Develop database Mx software for Cluster REC 4Q 04Establish a central database on Clinical Research 4Q 04Establish Study Site Guide & Investigator’s COP 4Q 04Investigator training & refreshing training on REC 1Q 05 -Develop on-line submission of application 3-4Q 05

APPROACH

Quality System Documentation

as backbone of Research Ethics practice

(& development) in HA

Why ?Why ?

Provides AnchorageProvides Anchorage

• Align structure, process & output requirements to policyAlign structure, process & output requirements to policy• Delineate responsibility / accountability of relevant Delineate responsibility / accountability of relevant

parties & personnelparties & personnel• Convert knowledge & accepted practices to institution Convert knowledge & accepted practices to institution

rulesrules

– Guide specific tasksGuide specific tasks

– Describe expectation on performance (competence)Describe expectation on performance (competence)

– Basis for training & auditBasis for training & audit

In-process Metrics for CQIIn-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)

Ensures ApplicabilityEnsures Applicability

• InternalizingInternalizing: convert knowledge & accepted practices : convert knowledge & accepted practices into institution rules (deliberation to adapt into local into institution rules (deliberation to adapt into local context)context)

– From generic to specific requirementsFrom generic to specific requirements

– Customize with system, expertise & resources Customize with system, expertise & resources (practical consideration)(practical consideration)

– Tailor requirement to audiences’ perspectives Tailor requirement to audiences’ perspectives (drafting skill for technical communication)(drafting skill for technical communication)

• ApprovalApproval: assign authority to document: assign authority to document

Assures Right InformationAssures Right Information

• To preclude use of obsolete documents, documents areTo preclude use of obsolete documents, documents are

– uniquely identifieduniquely identified

– filed in a readily accessible sourcefiled in a readily accessible source

– distributed to concerned personnel & workplaces distributed to concerned personnel & workplaces (consider web-based technology)(consider web-based technology)

– Obsolete document for archive is clearly denotedObsolete document for archive is clearly denoted

• Scheduled review to ensure continual validityScheduled review to ensure continual validity

QS documentation is especially important for:

• Large organization

• High stake activities―Narrow safety margin―Involves multi-parties―Labor intensive

3 Pillars Protecting3 Pillars Protecting Research SubjectsResearch Subjects

Protection Protection of Human of Human Research Research SubjectsSubjects

REC / IRBREC / IRB

Study Site AuthorityStudy Site Authority(hospital/ HA, University)(hospital/ HA, University)

InvestigatorsInvestigators(research team)(research team)

They have related but different roles They have related but different roles & responsibilities, thus require & responsibilities, thus require

correspondingly different guiding correspondingly different guiding documentsdocuments

Document Should Document Should Accommodate Audience’s PerspectiveAccommodate Audience’s Perspective

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

- 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 REC2. Review SAE reports3. Notify HA REC if SAE demands

study termination (Alert/Recall)

REC / IRBREC / IRB

Study SitesStudy Sites

1. Institute measures for early detection& Mx of possible adverse outcomes

InvestigatorsInvestigators

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

1. 1. REC / IRB Guide (internalizing good practices)REC / IRB Guide (internalizing good practices)

HA Guide forCluster REC

Established by HA REC:Established by HA REC:• HA-wide StandardsHA-wide Standards• Framework for SOP & Form Framework for SOP & Form

development in clustersdevelopment in clusters

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

InternationalInternationalrequirementsrequirements& practices& practices

Local regulation HA policy

Cluster REC Standard OperatingProcedure & Forms

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

Local requirements & practicesLocal requirements & practices

Declaration of Helsinki

2. 2. Investigator’s Code of PracticeInvestigator’s Code of Practice

Investigators have the Investigators have the primary responsibilityprimary responsibility for protecting the rights for protecting the rights & welfare of human research subjects. They must comply with all & welfare of human research subjects. They must comply with all applicable provisions, such asapplicable provisions, such as– Ethical responsibilityEthical responsibility– Right of participantsRight of participants– Consent to researchConsent to research– Regulatory requirements, professional standard, institutional Regulatory requirements, professional standard, institutional

policies & procedurespolicies & procedures– Relationship with external sponsorRelationship with external sponsor– Interaction with REC & study site administrationInteraction with REC & study site administration– Handling potential conflict of interestHandling potential conflict of interest

3. HA Study Site Guide3. HA Study Site Guide• All institutions involved in clinical research have a responsibility to All institutions involved in clinical research have a responsibility to

protect research participantsprotect research participants– Explicit policy & procedures on human protection in researchExplicit policy & procedures on human protection in research– Sufficient facilities & competent investigatorsSufficient facilities & competent investigators– Formal vetting & approval procedureFormal vetting & approval procedure– Study monitoring, esp. record management, SAE handling, Study monitoring, esp. record management, SAE handling,

complaint management, procedure to deal withcomplaint management, procedure to deal with incompetence incompetence & misconduct& misconduct

– Training, risk managementTraining, risk management– Interfaces with REC & HAHOInterfaces with REC & HAHO

Administrative procedures may be handled Administrative procedures may be handled differently from one institution to anotherdifferently from one institution to another

Level of Document InternalizationLevel of Document Internalization

HA level Cluster Level Hospital level

REC/IRB Guide+ + –

Investigator’s COP+ – –

Study Site Guide+ ± ±