CRP 112 Lecture 9 Flashcards
HC: Part C Division 5 Guidance
A tool to:
Help anyone involved in conduct of CTs to understand & comply
with Part C Div 5
Allow Health Canada to promote and enforce stakeholder
compliance with Part C, Division 5
Promote consistency & quality in the conduct of compliance
activities
-does not include medical devices, Natural health products or observational studies
C.05.010 (a): Sound Protocol
Compliance is determined at the time of review by the
appropriate directorate (TPD or BGTD) of HC (Protocol
scientifically sound & clearly described in a protocol)
C.05.010 (b): Follow protocol & regs
Sponsor must ensure CT sites follow approved protocol
Site must have system to ID, document, assess & report all PDs to
sponsor & REB when required
CT protocol is a study plan to ensure objectives of CT can be met
CT protocol standardizes a CT to allow for external validation &
generalization of CT results
CTs should be conducted according to ethical principles
C.05.010 (c): Systems & Procedures
Sponsor must establish a quality system of documented procedures (e.g.
SOPs) to assure quality of every aspect of CT through all stages and at
all sites as per regs and ICH E6
QMS should use risk-based approach as per ICH
QA and QC systems (ICH E6, 5.1.1)
CRO may have duties but responsibility with sponsor (5.2.1)
Duties must be in writing with sponsor ensuring oversight
Monitoring & Auditing
Processes to handle non-compliance documented in risk-based monitoring
plans
Monitor –written report after each site visit
Auditing – independent from monitoring or QC
Root cause analysis & CAPA action by sponsor
equiptment
Risk-based approach to ID critical equipment for CT
All equipment must be calibrated & maintained
FDA Risk based Monitoring Guidance
Monitoring plan describes:
Monitoring strategy
Monitoring responsibilities of all parties
Various monitoring methods to be used
Rationale for their use
Emphasize critical data & processes
Especially those not routine clinical practice
Reference ICH E6, 5.18.7
C.05.010(d): REB
No jurisdiction over how REBs conduct their operations or
establish SOPs
REB membership defined in section C.05.001 (Append. A)
HC recommends following: ICH E6, TCPS2, prov. standards
ICH E6 Section 3 describes REBs
C.05.010(e): QI
Licensed MD or dentist listed on QIU form
All tasks responsibility of QI unless delegation documented (DELEGATION LOG)
Complete prior to commencement of CT & updated as necessary
Clinical Trial Site Information Forms (CTSI)
C.05.010(f): Medical care/decisions
Sponsor designates qualified medical personnel (qualified MD or
Dentist) as the QI
QI to tell participant’s MD, with permission, about CT
QI must provide adequate medical care for AEs
Sponsor ensures medical care & decisions under supervision of QI
QI supervises CT staff
C.05.010(g):Individual qualifications
All individuals qualified by education, training & experience to perform their tasks
Sponsor must ensure individuals remain qualified during CT with documentation
QI ensures all staff trained on protocol, IP & duties
Training: relevant to CT & at minimum relevant sections of protocol for each individual and ICH E6 & Part C Div 5, all training must be documented
C.05.010(h): Informed Consent
Informed consent is a process (ICH E6 1.28)
Must inform re risks, inconveniences & benefits (4.8.10 g&h)
Risk/inconveniences must not outweigh benefits (2.2)
Rights/ safety & well being prevail over science & society (2.3)
ICF – written, signed & dated (1.28) & freely given (2.9)
No coercion or influence (4.8.3)
REB must approve all written info given to participants
QI must have documented SOP for IC process & site staff involved must be trained & comply with SOP
HC expects sponsors to demonstrate participant has read & understood entire ICF (e.g. Initial each page OR statement at end of ICF)
participants should be made
aware of important new information added to ICF as soon as
available as may affect willingness to participate
participant to sign amended ICF no later than next scheduled visit
Not capable of informed consent = assent
Minors, patients with severe dementia
Need written procedure (may be part of existing ICF SOP)
Must inform participant to best of their understanding (4.8.12)
Emergency situations (prior consent not possible) obtain consent from
participant’s Legally Acceptable Representative (defined provincially)
If LAR no available, protocol will describe required measures including REB approval & informing LAR ASAP
Electronic ICF acceptable if all regulatory & ICH requirements met, i.e. fully validated system
C.05.010(i): CT records
Sponsor ensures CT information recorded, handled & sorted to allow accurate reporting, interpretation & verification
C.05.010(j): GMP
Certificate of Analysis (CoA) of CT drug adequate evidence of
GMP compliance
Marketed drugs in CT must have NOC/DIN OR be a marketed
Canadian equivalent from acceptable foreign jurisdiction AND be used within
marketing authorization
All drugs on NOL are considered investigational
Drug must be traceable through sourcing, manufacturing,
packaging, storage, transport & delivery to CT site, administration
to participants, reconciliation and disposal/destruction
Storage & Transport conditions - use risk-based approach
Adequate labelling is essentia
C.05.011: Labelling
The label of the drug did not contain the
required information
C.05.012: Records
CT records had errors and/or missing information that did not allow
for complete and accurate reporting, interpretation, and verification
Sponsor did not ensure the edata system met requirements for
completeness, accuracy, and reliability
i.e. need proper records of everything and must have system to retain for 15 years
C.05.013: Submission of Info & Samples
Sponsor did not submit requested information concerning the drug
or the CT, and/or requested samples of the drug, within the
required time frame
C.05.014: SUADR
Sponsor did not inform HC within 15 days of
becoming aware of SUADR in or outside Canada
that were not fatal or life threatening
Sponsor did not inform HC within 7 days of becoming aware of
SUADR in or outside Canada that were fatal or life threatening
Sponsor did not submit a complete report with an assessment of its
findings within 8 days of informing HC of a fatal or life threatening
SUADR
C.05.015: Discontinuation of a CT
Sponsor did not inform HC within 15 days of a CT being
discontinued
Sponsor did not take reasonable measures to ensure return of all
unused quantities of drug (including participant returns) after a
CT was discontinued
What is CONSORT?
CONsolidated Standards Of Reporting Trials
Designed to alleviate problems arising from inadequate reporting of
randomized controlled trials
25-item checklist
Focus on design, analysis & interpretation
Flow diagram
Displays progress of all participants through trial
Abstract: Structured summary
Clear, transparent, and sufficiently detailed
Some readers use an abstract as a screening tool to decide whether
to read the full article
Healthcare decisions sometimes made on basis of abstracts of
randomised trials
Abstract: Accurate Record
Should contain sufficient information to serve as an accurate record
of study conduct and findings
Provide optimal information about trial within space constraints &
format of a journal
If properly constructed & written it:
helps individuals to assess quickly relevance of findings
aids retrieval of relevant reports from electronic databases
-do not omit harms
Abstract: Essential Items List
-authors
-trial design
-participants (eligibility)
-interventions
-objective
-primary outcome
-randomization
-blinding
-numbers randomized
-outcome
-harms
-conclusions
-trial registration number and register
