Transcript The monitoring process - presentation

The monitoring process
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
Stages of a monitoring visit
• Before the visit
• During the visit
• After the visit
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
During the visit
• The monitor will assess or discuss:
Site, staffing, research labs or other facilities
Regulatory file and study records
Clinical procedures if possible or appropriate
Any problems and issues identified
Debrief at end of visit
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
After the visit
• The monitor will
Complete site visit report
Submit the report to the sponsor
• The sponsor will:
• Distribute site visit report to the site
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
4 types of monitoring visits:
•
•
•
•
Site assessment(pre trial)
Site initiation
Routine(interim) visits)
Close out visit
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
Pre study visit
Purpose :
It’s a face to face meeting with the
investigator to explore the overall
feasibility of the site and the investigator to
participate into the study.
May be combined with the study initiation
visit.
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
Site assessment
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
Study initiation visit
• Purpose:
- to uniformly provide study specific
information to investigator(s) and study
staff prior to study start up.
- reassess resources and capability to
conduct a research study.
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
Study initiation(cont)
 The monitor will meet with the study staff to
discuss research obligations under GCP:
Investigator administrative responsibilities
IRB approvals and communications
Regulatory file requirements(ICH GCP E6 8.2)
Informed consent forms and process
Protocol and protocol amendments
Source documentation
Study product handling and accountability
Safety reporting
Protocol specific training
Archiving of study documents
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
Study initiation (cont)
• The monitor will
Review sponsor policies , standards and
procedures for the conduct of clinical trials.
Reassess the site facilities
Provide additional guidance to the site as
determined by his/her findings.
The better the site initiation, the better the site
performance.
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
Interim monitoring visits
Purpose:
 Protection of human subjects rights and
wellbeing.
 Accuracy, completeness and verification of
reported trial data.
 Trial conduct in compliance with
protocol/amendments, GCP and regulatory
requirements.
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
Interim visit (cont)
• Review /assess the following:
Enrollment status, rate and any drop outs.
regulatory files
CRF’s, source documents, informed consents,
AEs/SAEs/SUSARs
Study product
Protocol and regulatory compliance
laboratory review
clinical operations
• Follow up on previously identified issues
• Debrief
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
Source data verification process
Source data:
 all information in original records and certified copies of original
records of clinical findings, observations or other activities in a
clinical trial necessary for the reconstruction an evaluation of the
trial. (ICH GCP1.51)
Source documents:
 original documents, data and records(e.g. hospital records, lab
notes, clinical charts, subjects diaries, pharmacy dispensing
records, x-rays, subject files etc) (ICH GCP 1.52)
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
SDV process(cont)
 SDV: evaluation of the conformity of the data presented
in CRFs with source data.
 Main aim: confirm that the data collected is complete, accurate,
reliable and verifiable so as to give confidence to sponsor and
regulatory authorities in the data being used to support a
marketing application.
 Without SDV, no scientist can have confidence in data presented
and conclusions derived.
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
SDV process (cont)
Key data :
10 efficacy data
Inclusion/exclusion criteria
Medical/medication history
Physical exam/vital signs
visit dates
Adverse events
Concomitant medication
Record that patient entered clinical study and date of IC
Any gross errors in these might be detrimental to the
scientific and ethical quality of the clinical trial.
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
SDV process(cont)
Methods of SDV:
Back to back
Direct method- monitor has direct access to
source data (ICH GCP E6 1.21,5.15)
Extent of SDV ???
Depends on: clinical trial phase, quantity of data,
time availability, man power availability,
investigator research experience, company policy,
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
SDV process (cont)
 Common approach:
 Critical data: focal to aims and objectives of study and must be
correct.
 Informed consent to participate
 Clinical notes
 Conformance to inclusion/exclusion criteria
 Primary efficacy endpoints
 Secondary efficacy endpoints
 Recording and reporting of SAEs
 Documentation that that study drug was prescribed and at the
specified dosage
 Visit dates as per protocol
 Non-critical data e.g. very neat, high numbers of overwriting, rapid
recruitment, lack of SAEs when they would be expected etc.
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
SDV process(cont)
• CRF content review:
Missing, incomplete or illegible entries, signatures
or dates
Data recorded in wrong fields
Illogical, inconsistent or ambiguous data
Data omissions
Entries demonstrating failure to follow protocol
Inaccurate calculations
Inadequate documentation of corrections
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
SDV process(cont)
• Common problems
Data entered directly to CRF
Brief medical history/ scanty clinical notes
Several volumes of SD
SD/CRF mismatch
Illegible handwriting
Maximum acceptable error rate
• Document the SDV process
SD examined
CRFs checked and why they were selected
Critical and non-critical data items checked
Nature and frequency of errors
Any corrective actions undertaken
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008
Informed consent documents
• What to check:
Each participant has personally signed and dated ICD
prior to study procedures.
Appropriate use of independent witness
Correct version being used
Names of subjects/person giving consent, date and
time
Investigator appropriately signed ICD and dated.
All pages of ICD present
Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme
Version: 3-Nov-2008