ICH E6 – Guideline for Good Clinical Practice/GCP Flashcards
What is the objective of ICH GCP?
To provide a unified standard for the European Union, Japan, and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdiction
What should be weighed or considersed before a trial is initiated or continued?
Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks
What does ADR stand for?
Adverse drug reaction
What is the definition of ADR?
A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases
What ADRs should require expedite reporting?
The sponsor should expedite the reporting to all concerned investigator(s)/institutions(s), to the IRB(s)/IEC(s), where required, and to the regulatory authority(ies) of all adverse drug reactions (ADRs) that are both serious and unexpected.
What is an AE?
Adverse Event
What is the definition of an AE?
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a investigational product, whether or not related to the investigational product
When should AEs identified in the protocol be reported?
AE identified in the protocol as critical to safety evaluations should be reported to the sponsor according to the reporting requirements and within the time periods specified by the sponsor in the protocol
What is the definition of Blinding/Masking?
A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s).
Single Blinding
Single blinding usually refers to the subject(s) being unaware
Double Blinding
Double blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s)
What is a CRF?
Case Report Form
What is the definition of CRF?
Document designed to record all of the protocol required information to be reported to the sponsor on each trial subject
What is the definition of a Comparator?
An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial
T/F The investigator may implement a deviation from, or a change in, the protocol to eliminate an immediate hazard(s) to trial subjects without prior IRB/IEC approval/favorable opinion.
True, The investigator may implement a deviation from, or a change in, the protocol to eliminate an immediate hazard(s) to trial subjects without prior IRB/IEC approval/favorable opinion. As soon as possible, the implemented deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be submitted: To the IRB/IEC for review and approval/favorable opinion; To the sponsor for agreement and, if required to the regulatory authority(ies).
Coordinating committee?
A committee that a sponsor may organize to coordinate the conduct of a multicenter trial.
DSMB/DSMC
An independent data monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial.
Audit
Audit is a systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted, and the data were recorded, analyzed, and accurately reported according to the protocol, sponsor’s standard operating procedures (SOPs), good clinical practice (GCP), and the applicable regulatory requirement(s).
Inspection
Inspection 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
How long should Essential Documents be retained for?
Essential Documents should be retained until at least 2-years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period, however, if required by the applicable regulatory requirements or by an agreement with the sponsor.
Whose responsibility is it to inform the investigator/institution as to when essential documents no longer need to be retained?
It is the responsibility of the sponsor to inform the investigator/institution as to when these documents no longer need to be retained
ICF should not contain any language that causes subject or the LAR from…
ICF should not contain any language that causes the subject or the LAR to waive or to appear to waive any legal rights.
Who needs to sign the ICF?
ICF should be signed and personally dated by the subject or by LAR, and by the person who conducted the informed consent discussion
If a subject or LAR is unable to read, what should happen?
If subject is unable to read or if a legally acceptable representative is unable to read, an impartial witness should be present during the entire informed consent discussion.
By signing the consent form, what does the witness attest to?
By signing the consent form, the witness attests that the information in the consent form and any other written information was accurately explained to, and apparently understood by, the subject or the LAR, and that informed consent was freely given by the subject or the subject’s legally acceptable representative.
T/F In emergency situations, when prior consent of the subject is not possible, the consent of the LAR, if present, should be requested.
True
When prior consent of the subject is not possible, and the LAR is not available, what should occur?
When prior consent of the subject is not possible, and the LAR is not available, enrollment of the subject should require measures described in the protocol and/or elsewhere, with documented approval/favorable opinion by the IRB/IEC, to protect the rights, safety and well-being of the subject and to ensure compliance with applicable regulatory requirements. The subject or LAR should be informed about the trial as soon as possible and consent to continue and other consent as appropriate should be requested.
What is the definition of IRB?
An independent body constituted of medical, scientific, and nonscientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trial protocols and amendments and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects.
How many members does an IRB have?
At least 5
What documents should the IRB obtain? (7)
- Trial protocol(s)/amendment(s),
- Written informed consent form(s) and consent form updates that the investigator proposes for use in the trial,
- Subject recruitment procedures (e.g., advertisements), written information to be provided to subjects,
- Investigator’s Brochure (IB),
- Available safety information,
- Information about payments and compensation available to subjects,
- Investigator’s current curriculum vitae and/or other documentation evidencing qualifications, and any other documents that the IRB/IEC may need to fulfill its responsibilities
What are possible IRB Outcomes?
- Approval/favorable opinion
- Modifications required prior to its approval/favorable opinion
- Disapproval/negative opinion
- Termination/suspension of any prior approval/favorable opinion
How often should continuing reviews be conducted?
IRB/IEC should conduct continuing review of each ongoing trial at intervals appropriate to the degree of risk to human subjects, but at least once per year
T/F Payments to a subject are based on the completion of the trial by the subject
Payments to a subject should be prorated and not wholly contingent on completion of the trial by the subject
T/F The investigator may provide information on any aspect of the trial but should not participate in the deliberations of the IRB/IEC or in the vote/opinion of the IRB/IEC.
True
Who should the IRB be composed of?
- At least five members.
- At least one member whose primary area of interest is in a nonscientific area.
- At least one member who is independent of the institution/trial site.
What 4 things require prompt reporting to the IRB/IEC from the PI?
- Deviations from, or changes of, the protocol to eliminate immediate hazards to the trial subjects
- Changes increasing the risk to subjects and/or affecting significantly the conduct of the trial
- All adverse drug reactions (ADRs) that are both serious and unexpected.
- New information that may affect adversely the safety of the subjects or the conduct of the trial.
What are things the IRB notifies the PI about?
- Its trial-related decisions/opinions
- The reasons for its decisions/opinions
- Procedures for appeal of its decisions/opinions
How long should the IRB/IEC should retain all relevant records of a trial?
The IRB/IEC should retain all relevant records (e.g., written procedures, membership lists, lists of occupations/affiliations of members, submitted documents, minutes of meetings, and correspondence) for a period of at least 3 years after completion of the trial
Who is responsible for the conduct of the clinical trial at a trial site?
An investigator
IRB approval of what (3) things is required by the investigator/institution before initiating a trial?
Before initiating a trial, the investigator/institution should have written and dated approval/favorable opinion from the IRB/IEC for the trial protocol, written informed consent form, subject recruitment procedures