Transcript Slide 1

Quality System Documentation
for
Research Ethics
Clinical Effectiveness Unit
Division, PS & MD
2005
BACKGROUND
HK has no Statute specifically on clinical
research
Ethical oversight relies on
– Professional self-discipline
– Administrative control of academia &
healthcare providers
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
Research Ethics in HA: Past
19921994
19952001
Infrastructure
1 Ethics Committee
at HAHO replaced
HSD/DH’s EC
Progress
Inherited existing practice
Mandatory ethical review
University’s IRB/EC
(teaching hospitals)
Compliance with applicable
regulatory requirements &
Declaration of Helsinki
Set up hospital-based
ECs (up to 42 at year
2001)
Expanded review capacity
to cope with increasing
research activities
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
Insufficient enforcement mechanism
Performance did not meet ICH-GCP standard,
a prerequisite for international drug trials
Research Ethics in HA: Present
Infrastructure
2002- 2-tier structure
- HA REC (standard
setting, compliance
oversight, appeal)
- Consolidated 42 Hosp
ECs to 6 Cluster RECs
(ethical review, study
oversight)
- HA & CU, HKU
merged their
respective RECs in
2002
Progress
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
- harmonize practices (HA &
medical schools)
- meet global development
- enable compliance oversight
Quality System Documentation
as the backbone of Research Ethics
practice (& development) in HA
Importance of Documentation System
Internalize ethical principles & global best practices
into explicit “HA standards”
Enforceability
Provide clear expectations on performance
Align system & process to policy
Assure consistent, impartial & transparent processes
Delineate ethical responsibilities
Facilitate communication, feedback, training &
compliance oversight
Documentation sustains Enforceability
Document
generation
Validation
Approval
Standardized
record forms
Dissemination,
training
Document
control
Document
maintenance
Engage (empower) operators to review current
practice & system
Internalize knowledge & accepted practices
into institution rules
Ensure alignment to policy & achievability
Assign authority (& necessary system support)
Provide audit trails on control critical events
Inform & equip relevant personnel
Ensure right (update) information
Ensure continual suitability
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
Procedural justice
Facilitate communication, feedback, training &
compliance oversight
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 必須有目共睹
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
Practice point: Corrections made in document must
be crossed out (still see through), initialled & dated
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
Sharing ethical responsibilities
Facilitate communication, feedback, training &
compliance oversight
Sharing Ethical Responsibilities
Dept of Health
Sponsors
Medical Council
Global references
• IDMC
• Site audit
Research Organizations
HA’s
Hospital Authority • Policy & Standards
jurisdiction
• Compliance oversight
HA REC
• Investigator privilege
• Study site facilities
• Clinical trial
agreement
• Indemnity agreement
• Risk Mx, insurance
• Handle complaints &
malpractice
• Training
• Appeal (REC decision)
Study Site Administration
CUHK, HKU
Medical Faculty
Policy & requirements
on research
Study Site
Administration
University
Non-teaching
Teaching hospitals
facilities
hospitals
CU / HKU REC
Cluster REC
Investigators
Research
subjects
• Gate keeping
• Ethical review
• Study oversight
• AE oversight
• Progress reports
Investigators
Research subjects
HA
Non-HA
patients
patients
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
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
HA delivers research ethics through
HA REC
Cluster RECs
Research
Subject
Protection
Investigators
Hospital
(Study Sites)
Administration
by adopting a Quality System approach
Corresponding to the parties
involved, there are 3 Guiding
Documents
& a number of forms
Documents accommodate Different
Obligations & Audience Perspectives
REC / IRB
1. Study oversight requires prompt
SAE reporting to REC
2. Review all SAE reports
3. Alert HA REC if SAE demands
study termination
e.g. on
handling
SAE
Study Sites
1. Ensure investigator competence
2. Administrative oversight & legal
support
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)
3. Update participants (& consent
form) if the SAE is relevant to
subjects’ willingness to participate
1. REC Guide (internalizing best practices)
Local standards & practices
Established by Cluster REC:
Cluster REC
Standard Operating • Guides operation
• Enables audit
Procedure & Forms
ICH GCP (E6)
Other references,
e.g. FDA IRB Guide
Established by HA REC:
• HA-wide Standards
HA Guide for • Guiding document for Cluster
Cluster REC REC
• Enables audit
• Basis for harmonizing with CU
& HKU
International
requirements
& practices Declaration of Helsinki
Applicable regulations
Professional Code & Conduct
HA policy
Local requirements
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
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
Document Internalization within Organization
HA level Cluster Level Hospital level
REC Guide
+
+
–
Investigator’s COP
+
–
–
Study Site Guide
+
±
±
QS documentation is especially important for:
 Large
organization
 Activities
― high
characterized by
stake (narrow safety margin,
serious consequences)
― multi-parties
― labor
involvement
intensive processes