Lecture 2.2 clinical investigator Flashcards
Who is a clinical investigator according to ICP GCP definition?
A person responsible for the conduct of the clinical trial at a trial site
ICH suggests an investigator at each site; multisite study may have a coordinating investigator, but there should be a responsible party at each site
True or false.
True
What is the definition of a subinvestigator according to the defnition laid out by ICH?
Any individual member of the clinical trial team designated and supervised by the investigator at a trial site to perform critical trial-related procedures and/or make important trial-related decisions
Are the investigator contract out any of his responsibilities?
No
What are some responsibilities of the investigator?
- Communicate with the IEC/IRB
- Ensure proper informed consent
process - Protocol compliance
- Control of investigational products
- Maintenance of randomization and
blinding - Safety reporting
- Recordkeeping (case histories)
- Medical care of study subjects
- ensure qualifications and training of
study staff
What kind of reporting is required of an investigator?
Safety reports
Progress reports (to sponsor and IEC)
Final report
Under what circumstances can ‘unblinding’ occur?
for medical emergencies, must be documented
Under what circumstance can the investigator deviate from the protocol?
to eliminate an immediate hazard to subjects
Protocol should be designed to facilitate ___________.
compliance
Who shall the investigator report to when serious and unexpected event takes place?
sponsor, IEC/IRB and regulatory bodies
What is the main role of IEC?
- Safeguarding the dignity, right, safety and well being of all
acutal or potential research participants - Providing independent, competent, and timely ethical review of the proposed study
- Considering both the scientific and ethical aspects of the study – since scientifically unsound research is not ethical
What rights to subjects have?
- be informed
- not participate
- withdraw at any time
- protection of their privacy
What shall constitute the IEC?
- members must be diverse and independent
- at least 5 members
- at least one from non-scientific area
- at least one independent institution/study site
- non-voting experts may be invited as necessary
Who reviews investigator’s qualifications and ability to supervise and conduct the study?
IEC
Who is responsible for reviewing target subject population to ensure adequate inclusion/exclusion criteria and proper recruiting?
IEC
Who is responsible for reviewing proposed compensations to investigator and subjects?
IEC
Name some to-dos for IEC decision making process.
- No one with conflict of interest shall participate
- non-members excluded from deliberations and vote
- method of reaching decision pre-determined
At what intervals during the clinical study shall the IEC review the study/review?
As appropriate to risk of study, but at least annually
For how long are the study documents maintained by the IEC?
for at least 2 years after the study or latest approval
What concerns are raised if GCP is not followed?
- The subjects who take part may be exposed to increased risk
- The rights of the subjects may be violated
- The data collected may be unreliable
- The study could be rejected by regulatory agencies
What is meant by ‘audit’?
A systematic and independent examination of trial related activities and documents to
determine whether the evaluated trial related
activities were conducted, and data were recorded, analysed and accurately reported according to the protocol, sponsor’s standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory
requirement(s)
What is inspection?
The act by a regulatory authority(ies) of conducting an official review of documents,
facilities, records, and any other resources that are deemed by the authority(ies) to be related
to the clinical trial and that may be located at the site of the trial, at the sponsor’s and/or contract research organization’s (CRO’s)
facilities, or at other establishments deemed
appropriate by the regulatory authority(ies)
FDA Quality Standards for Clinical Study Data Must meet with the A-L-C-O-A concept.
What is ALCOA?
- Attributable (docs marked with appropriate identifiers)
- Legible (readable)
- Contemporaneous (data/findings/observations recorded at time they are generated)
- Original (first place where data is recorded)
- Accurate
What is the purpose of phase I clinical trials?
PK & PD data
dose finding
dose safety data
–> healthy subject used
What is the purpose of phase II clinical trials?
prove of concept
Whay kind of study could be conducted in phase II?
Simple single arm open label study or
two arms comparative study
What is meant by single arm open label study?
single arm = all participants receive same treatment, no control group
open label = no blinding,
What is the purpose and characteristic of phase III clinical trials?
Large scale study/ies
Double blind
Randomized design
Statistical significant
What is the purpose of phase IV clinical trials?
Extended Ph III study
LT safety FU
Post-marketing
surveillance
At which phase of the clinical trials is double blind study carried out?
Phase III
Should the protocol be finalised before the clinical trail stage commences?
Yes
‘Site closeout’ activities may include:
Final drug accountability
Drug return or local destruction
Site Closeout visit
Document archive and retention
PI submits End of Study report to IRB/EC
Does the PI need to submit end of study report to IEC after trials have finished?
Yes
What are the most common deficiencies in study trials?
- Protocol deviations
- Inadequate recordkeeping
- Inadequate accountability for the investigational product
- Inadequate subject protection – including informed consent issues
What are the most common IRB/IEC deficiencies?
- Inadequate initial and/or continuing review
- Inadequate SOPS
- Inadequate membership rosters
- Inadequate meeting minutes
What are some IP non-compliance issues that are exposed through regulatory inspections?
- temperature of IP out of range
- inadequate temperature monitoring
- access to/security of IP storage
