ICH E6 – Guideline for Good Clinical Practice/GCP Flashcards
(100 cards)
1
Q
What is the objective of ICH GCP?
A
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
2
Q
What should be weighed or considersed before a trial is initiated or continued?
A
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
3
Q
What does ADR stand for?
A
Adverse drug reaction
4
Q
What is the definition of ADR?
A
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
5
Q
What ADRs should require expedite reporting?
A
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.
6
Q
What is an AE?
A
Adverse Event
7
Q
What is the definition of an AE?
A
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
8
Q
When should AEs identified in the protocol be reported?
A
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
9
Q
What is the definition of Blinding/Masking?
A
A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s).
10
Q
Single Blinding
A
Single blinding usually refers to the subject(s) being unaware
11
Q
Double Blinding
A
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)
12
Q
What is a CRF?
A
Case Report Form
13
Q
What is the definition of CRF?
A
Document designed to record all of the protocol required information to be reported to the sponsor on each trial subject
14
Q
What is the definition of a Comparator?
A
An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial
15
Q
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.
A
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).
16
Q
Coordinating committee?
A
A committee that a sponsor may organize to coordinate the conduct of a multicenter trial.
17
Q
DSMB/DSMC
A
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.
18
Q
Audit
A
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).
19
Q
Inspection
A
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
20
Q
How long should Essential Documents be retained for?
A
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.
21
Q
Whose responsibility is it to inform the investigator/institution as to when essential documents no longer need to be retained?
A
It is the responsibility of the sponsor to inform the investigator/institution as to when these documents no longer need to be retained
22
Q
ICF should not contain any language that causes subject or the LAR from…
A
ICF should not contain any language that causes the subject or the LAR to waive or to appear to waive any legal rights.
23
Q
Who needs to sign the ICF?
A
ICF should be signed and personally dated by the subject or by LAR, and by the person who conducted the informed consent discussion
24
Q
If a subject or LAR is unable to read, what should happen?
A
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.
25
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.
26
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
27
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.
28
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.
29
How many members does an IRB have?
At least 5
30
What documents should the IRB obtain? (7)
1. Trial protocol(s)/amendment(s),
2. Written informed consent form(s) and consent form updates that the investigator proposes for use in the trial,
3. Subject recruitment procedures (e.g., advertisements), written information to be provided to subjects,
4. Investigator’s Brochure (IB),
5. Available safety information,
6. Information about payments and compensation available to subjects,
7. 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
31
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
32
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
33
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
34
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
35
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.
36
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.
37
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
38
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
39
Who is responsible for the conduct of the clinical trial at a trial site?
An investigator
40
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
41
Who is responsible for IP accountability at the trial site?
Investigator/institution
42
When it comes to IP, what should the PI/Pharmacist maintain records of?
PI/Pharmacist should maintain records of the product’s delivery to the trial site, the inventory at the site, the use by each subject, and the return to the sponsor or alternative disposition of unused product(s).
43
How should IP be stored?
IP should be stored as specified by the sponsor (and in accordance with applicable regulatory requirement(s).
44
When it comes to IP, what does the sponsor determine?
The sponsor should determine, for the investigational product(s), acceptable storage temperatures, storage conditions (e.g., protection from light), storage times, reconstitution fluids and procedures, and devices for product infusion
45
Who is responsible for supplying the investigator(s)/institution(s) with the investigational product(s)?
The sponsor
46
When it comes to IP what are the sponsor's main responsibilities? (6)
- Ensure timely delivery of investigational product(s) to the investigator(s).
- Maintain records that document shipment, receipt, disposition, return, and destruction of the investigational product(s)
- Maintain a system for retrieving investigational products and documenting this retrieval (e.g., for deficient product recall, reclaim after trial completion, expired product reclaim).
- Maintain a system for the disposition of unused investigational product(s) and for the documentation of this disposition.
- Take steps to ensure that the investigational product(s) are stable over the period of use.
- Maintain sufficient quantities of the investigational product(s) used in the trials to reconfirm specifications, should this become necessary, and maintain records of batch sample analyses and characteristics.
47
Who is responsible for the ongoing safety evaluation of IP?
The sponsor
48
How is IP implemented in a blinded trial?
Through a coding system. In blinded trials, the coding system for the investigational product(s) should include a mechanism that permits rapid identification of the product(s) in case of a medical emergency, but does not permit undetectable breaks of the blinding
49
What is an investigator's brochure?
A compilation of the clinical and nonclinical data on the investigational product(s) that is relevant to the study of the investigational product(s) in human subjects
50
What is the purpose of an investigator's brochure?
Its purpose is to provide the investigators and others involved in the trial with the information to facilitate their understanding of the rationale for, and their compliance with, many key features of the protocol, such as the dose, dose frequency/interval, methods of administration: and safety monitoring procedures.
51
T/F The investigator's brochure provides insight to support the clinical management of the study subjects during the course of the clinical trial.
True
52
Who is responsible for ensuring that an up-to-date IB is made available to the investigator(s)?
The sponsor
53
In the case of an investigator sponsored trial, who determines whether a brochure is available from the commercial manufacturer?
In the case of an investigator sponsored trial, the sponsor-investigator should determine whether a brochure is available from the commercial manufacturer
54
What should the information in an investigator brochure be based upon?
The investigator brochure be based should be based on the available physical, chemical, pharmaceutical, pharmacological, toxicological, and clinical information on the investigational product(s). Guidance should also be provided to the clinical investigator on the recognition and treatment of possible overdose and adverse drug reactions that are based on previous human experience and on the pharmacology of the investigational product
55
What is a LAR?
Legally Acceptable Representative
56
What is the definition of a LAR?
An individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subject’s participation in the clinical trial.
57
The ICF should not contain any information that that releases or appears to release the investigator, the institution, the sponsor, or their agents from…
The ICF should not contain any information that that releases or appears to release the investigator, the institution, the sponsor, or their agents from liability for negligence
58
What is the benefit of centralized monitoring processes?
Centralized monitoring processes provide additional monitoring capabilities that can complement and reduce the extent and/or frequency of on-site monitoring and help distinguish between reliable data and potentially unreliable data
59
What is a Non-Therapeutic Trial?
A trial in which there is no anticipated direct clinical benefit to the subject
60
When can nontherapeutic trials be conducted in subjects with consent of a LAR? (4)
Nontherapeutic trials may be conducted in subjects with consent of a LAR if:
- Objectives of the trial cannot be met by means of a trial in subjects who can give informed consent personally
- The foreseeable risks are low
- The negative impact on the subject’s well-being is minimized and low
- IRB/IEC is expressly sought on the inclusion of such subjects, and the written approval/ favorable opinion covers this aspect
61
If the investigator terminates or suspends a trial without prior agreement of the sponsor, who should be informed?
If the investigator terminates or suspends a trial without prior agreement of the sponsor, the investigator should inform the institution, and should promptly inform the sponsor and the IRB/IEC
62
If the sponsor terminates or suspends a trial, who should be informed?
The sponsor should promptly inform the investigators/institutions, and the regulatory authority(ies) of the termination or suspension and the reason(s) for the termination or suspension. The IRB/IEC should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor or by the investigator/institution,
63
If the IRB/IEC terminates or suspends its approval/favorable opinion of a trial, who should be informed?
If the IRB/IEC terminates or suspends its approval/favorable opinion of a trial, the investigator/institution should promptly notify the sponsor and provide the sponsor with a detailed written explanation of the termination or suspension.
64
What are progress reports and how often should they be submitted?
The investigator should submit written summaries of the trial’s status to the IRB/IEC annually, or more frequently, if requested by the IRB/IEC
65
What general information should the protocol include? (8)
- Protocol title
- Protocol identifying number
- Date
- Name and address of the sponsor and medical monitor
- Name and title of the person(s) authorized to sign the protocol and the protocol amendment(s) for the sponsor
- Name, title, address, and telephone number(s) of the sponsor's medical expert
- Name and title of the investigator(s) who is (are) responsible for conducting the trial, and the address and telephone number(s) of the trial site(s).
- Name(s) and address(es) of the clinical laboratory(ies) and other medical and/or technical department(s) and/or institutions involved in the trial
66
What is the definition of Quality Assurance?
Planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded), and reported in compliance with GCP and the applicable regulatory requirement(s)
67
Who is responsible for implementing and maintaining quality assurance and quality control systems?
The sponsor is responsible for implementing and maintaining quality assurance and quality control systems with written SOPs to ensure that trials are conducted and data are generated, documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory requirement(s)
68
Who is responsible for securing agreement from all involved parties to ensure monitoring and auditing?
The sponsor is responsible for securing agreement from all involved parties to ensure direct access to all trial-related sites, source data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and inspection by domestic and foreign regulatory authorities.
69
What is the definition of Quality Control?
The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial-related activities have been fulfilled
70
T/F Quality control should be applied to the final stage of data handling to ensure that all data are reliable and have been processed correctly.
False, Quality control should be applied to each stage of data handling to ensure that all data are reliable and have been processed correctly.
71
What is risk identification?
The sponsor should identify risks to critical trial processes and data. Risks should be considered at both the system level and clinical trial level (e.g., trial design, data collection, and informed consent process).
72
What is risk evaluation?
The sponsor should evaluate the identified risks, against existing risk controls by considering: The likelihood of errors occurring. (b) The extent to which such errors would be detectable. (c) The impact of such errors on human subject protection and reliability of trial results.
73
The sponsor should decide which risks to reduce and/or which risks to accept. The approach used to reduce risk to an acceptable level should be proportionate to the significance of what?
Risk control
74
What should be established to identify systematic issues that can impact subject safety or reliability of trial results?
Predefined quality tolerance limits
75
What describes when the sponsor communicates quality management activities to those who are involved in or affected by such activities, to facilitate risk review and continual improvement during clinical trial execution?
Risk communication
76
When the sponsor periodically reviews risk control measures to ascertain whether the implemented quality management activities remain effective and relevant, taking into account emerging knowledge and experience, what are they conducting?
Risk review
77
What is the sponsors description of the quality management approach implemented in the trial and the summary of important deviations from the predefined quality tolerance limits and remedial actions taken in the clinical study report?
Risk reporting
78
What is the definition of an SAE/SDR?
Any untoward medical occurrence that at any dose:
- Results in death
- Is life-threatening
- Requires inpatient hospitalization or prolongation of existing hospitalization
- Results in persistent or significant disability/incapacity
- Is a congenital anomaly/birth defect
79
When should SAEs be reported?
All SAEs should be reported immediately to the sponsor except for those SAEs that the protocol or other document (e.g., Investigator's Brochure) identifies as not needing immediate reporting.
80
How should reports identify subjects?
Immediate and follow-up reports should identify subjects by unique code numbers assigned to the trial subjects rather than by the subjects' names, personal identification numbers, and/or addresses.
81
T/F For reported deaths, the investigator does not need to supply the sponsor and the IRB/IEC with any additional requested information (e.g., autopsy reports and terminal medical reports)
False
82
What is the definition of 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 and evaluation of the trial. Source data are contained in source documents
83
What is the definition of a source document?
Original documents, data, and records e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate copies, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories and at medico-technical departments involved in the clinical trial
84
Define ALCOA-C
Source data should be attributable, legible, contemporaneous, original, accurate, and complete. Changes to source data should be traceable, should not obscure the original entry, and should be explained if necessary (e.g., via an audit trail) (ALCOA-C)
85
What needs to be done when changing or correcting a CRF?
Any change or correction to a CRF should be dated, initialed, and explained (if necessary) and should not obscure the original entry (i.e., an audit trail should be maintained); this applies to both written and electronic changes or corrections.
Sponsors should have written procedures to assure that changes or corrections in CRFs made by sponsor's designated representatives are documented, are necessary, and are endorsed by the investigator.
86
What is the definition of a sponsor?
An individual, company, institution, or organization that takes responsibility for the initiation management, and/or financing of a clinical trial.
87
What is the definition of a sponsor-investigation?
An individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a subject.
The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.
88
What is the definition of a Sub-I?
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 to make important trial-related decisions
89
What are the elements that should be included in trial design? (15)
- Primary endpoints and the secondary endpoints
- Type/design of trial (e.g., double-blind, placebo-controlled, parallel design) and a schematic diagram of trial design, procedures, and stages.
- Measures taken to minimize/avoid bias, including Randomization or Blinding
- A description of the trial treatment(s) and the dosage and dosage regimen of the investigational product(s)
- The expected duration of subject participation, and a description of the sequence and duration of all trial periods, including follow-up
- A description of the "stopping rules" or "discontinuation criteria"
- Accountability procedures for the investigational product(s), including the placebo(s) and comparator(s)
- Maintenance of trial treatment randomization codes and procedures for breaking codes
- The identification of any data to be recorded directly on the CRFs
- Subject inclusion/exclusion criteria
- The treatment(s) to be administered, including the name(s) of all the product(s), the dose(s), the dosing schedule(s), the route/mode(s) of administration, and the treatment period(s), including the follow-up period(s) for subjects for each investigational product treatment/trial treatment group/arm of the trial
- Medication(s)/treatment(s) permitted (including rescue medication) and not permitted before and/or during the trial
- Assessment of Efficacy
- Assessment of Safety
- Statistics
90
What is the definition of an UAE?
Unexpected adverse event. An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator’s Brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product)
91
Who are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate?
Vulnerable subjects
92
Who are examples of vulnerable subjects?
Examples are members of a group with a hierarchical structure, such as:
- medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry,
- members of the armed forces
- persons kept in detention
- patients with incurable diseases, persons in nursing homes,
- unemployed or impoverished persons,
- patients in emergency situations,
ethnic minority groups,
- homeless persons, nomads, refugees, minors,
- those incapable of giving consent.
93
Definition of accurate
consistent and real representation of facts
94
Definition of original
Exact copy or first record made by the appropriate person.
95
Definition of contemporaneous
Information should be documented in the correct time frame along with the flow of events.
96
Definition of Legible
Readable and signatures are identifiable
97
Definition of Attributable
Clear who has documented the data
98
REMS
Risk Evaluation Mitigation Strategies - utilized to ensure the drug's benefits outweigh the risks
99
Term used to indicate that a determination has been made that the event had a reasonable possibility of being related to exposure to the product
Relatedness
100
What should support the delegation of authority log?
- signed/dated CVs
- evidence of contract with the host site
- training certifications
- attendance and notes from study initiation
- SOP signature pages
