Clinical Trials and Quality Assurance Flashcards
(124 cards)
1
Q
What is a clinical trial?
A
Biomedical or health-related scientific experiment designed to answer specific question(s)
2
Q
What is the difference between a clinical trial and a clinical study?
A
Clinical trials are prospective whereas clinical studies can be both prospective and retrospective
3
Q
What are some study designs?
A
Experimental (interventional):
Semi-experimental
Observational (non-interventional)
4
Q
What is an experimental study?
A
Evaluates efficacy (explanatory) and effectiveness (pragmatic) of a therapeutic or treatment
5
Q
What is a semi-experimental study?
A
Trials with historical controls
6
Q
What is an observational study?
A
Subjects observed and specific outcomes measured without any active intervention of the subjects’ medical care
No experiment is being performed
7
Q
What are some types of experimental clinical trials?
A
Diagnostic
Screening
Quality of Life
8
Q
What is a diagnostic clinical trial?
A
Evaluates the ability of a test or procedure to correctly diagnose a disease or medical condition or to measure a specific parameter
9
Q
What is a screening clinical trial?
A
Tests the best way to detect certain diseases or health conditions
10
Q
What is a quality of life clinical trial?
A
Measure effect on quality of life or changes in behaviors or lifestyle factors
11
Q
What is the difference between efficacy and effectiveness?
A
Efficacy = explanatory Effectiveness = pragmatic
12
Q
What is efficacy?
A
Measure product’s ability to treat the indicated condition
Tests whether the product produces the desired clinical outcome under research (or optimal) conditions
13
Q
What is effectiveness?
A
Measure of how well the drug or device works; includes efficacy as well as the tolerability and ease of use of the product
Focuses on whether an intervention or procedure works under usual conditions or actual practice
14
Q
Why are interventional clinical trials needed?
A
Definitive method and provides sounder rationale for determining an intervention’s effect
Helps determine incidence of AE or complications of intervention
Clinical practice influence
15
Q
What are some types of interventions?
A
Single/individual treatment/therapy Exposure (i.e. radiotherapy) Medical device Surgical technique Combination treatment Educational or behavioral program Dietary change
16
Q
What is clinical research? What of the individual subject?
A
Goal: to test a hypothesis and generate knowledge to improve medical care or public health; serve the common good
Individual subject may or may not benefit from participation
17
Q
What is clinical practice? What of the individual subject?
A
Goal: diagnose, provide preventative care, or treat illness or medical condition in a particular individual(s) with reasonable expectation of success
Care provided to enhance individual patient’s well-being
18
Q
T/F: High quality care and treatment for the patient is the goal of clinical research?
A
F
19
Q
When was the concept of blindness introduced and by whom?
A
1931
Amberson via flip of a coin as a form of random treatment group assignment
20
Q
When was the importance of controlled experiments emphasized and by whom?
A
1930
Sollman
21
Q
When was the Nuremberg Code created and in reaction to which event?
A
1949
to the Nazi human experimentations
22
Q
When was the Federal Food, Drug, and Cosmetic Act and what did it entail?
A
1962
required informed consent and that subjects be told if the drug is investigational
23
Q
When was the Declaration of Helsinki and what did it entail?
A
1964
stressed importance of assessing risks vs potential benefits of clinical research
24
Q
What is IRB and when was it established?
A
Institutional Review Board: reviews all clinical research performed under Public Health Service grants
1966
25
What is a benefit to clinical research?
Enables advances in medical practice and healthcare that otherwise would not be possible
26
What are some limits to clinical research?
Rigorous conduct required to avoid false results could cause harm
Individual subjects may or may not benefit
Opportunity for exploitation when subjects are exposed to potential risks for benefit of others/society
27
What are some historical violations of human rights?
Nazi War Crimes
Brooklyn Jewish Chronic Disease Hospital (1963)
Hepatitis B study at Willowbrook
Tuskegee syphilis study (1932-1972)
28
What documents have helped shape the current ethical framework for human research studies conduct?
Nuremberg Code
Declaration of Helsinki
Belmont Report
29
When was the Declaration of Helsinki established and what did it entail?
1964
| Recommendations to be used as an ethical code by all medical doctors conducting biomedical research
30
When was the Belmont Report established and what did it entail?
1979
| Emphasizes need to protect human subjects from exploitation and harm
31
What are the basic ethical principles that guide the conduct of research?
Respect for persons
Beneficence
Justice
32
What is respect for persons?
Individuals should be treated as autonomous
| Some persons are in need of protection (and may even need to be excluded from potential harm)
33
What is beneficence?
Study has social/scientific value, scientific validity, and favorable risk/benefit ratio
Do not harm
Maximize potential benefits and minimize potential harms
34
What is justice?
Recruitment and selection of subjects is fair and inclusion/exclusion criteria are reasonable
Selection should not be based on easy availability, compromised position, manipulability
35
What elements does informed consent contain?
Information
Comprehension
Voluntariness
36
What is the ethical framework for clinical research?
```
Value
Validity
Fair subject selection
Favorable risk-benefit ratio
Independent review
Informed consent
Respect for enrolled participants
```
37
Who is the end customer?
Patient
38
What is the purpose of a clinical trial?
Assess safety and efficacy/effectiveness
Develop package insert or instructions/directions for use
Enable safe and effective use of the product by HCP and/or patient
39
What is the FDA mission?
Protect and promote public health through safety, efficacy, and security of products regulated
40
What is the FDA's definition of a drug?
An article intended for use in the diagnosis, cure, mitigation, treatment, or prevention of a disease
An article intended to affect the structure or any function of the body
41
What is the FDA's definition of a biologic?
Virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or rasphenamine or derivative of arsphenamine, applicable to the prevention, treatment, or cure of a disease or condition of human beings
42
What is the FDA's definition of a medical device?
Instrument, apparatus, implement, machine, implant, in vitro reagent which is intended for use in diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, or which is intended to affect the structure or function of the body
43
What is the FDA's definition of a combination product?
Product comprised of two or more regulated components that are physically, chemically, or otherwise combined or mixed and produced as a single entity
Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products
44
What is CDER?
Center for Drug Evaluation and Research
| Regulates new molecular entities (NMEs)/chemically synthesized drugs
45
What is CDRH?
Center for Devices and Radiological Health
| Regulates manufacturing, performance, and safety of medical devices and radiation-emitting products
46
What are the classes of medical devices?
Class 1, 2, and 3
47
What is a class 1 device?
Everyday items which are unlikely to cause serious consequence if they fail
48
What is a class 2 device?
"Medium risk" such as demineralized bone powder
49
What is a class 3 device?
Products which would cause obvious risk of injury or death if they don't function properly
Require pre-market approval (PMA)
50
What is CFR and which pertains to drugs?
Code of Federal Regulations
| Title 21
51
What are guidance documents?
Describe the FDA's current thinking on, interpretation of, or policy on, a regulatory issue
Intended to help the "public" understand and comply with regulations and laws
52
T/F: Guidance documents are legally binding.
F
53
What is 21 CFR 312?
Investigational new drugs regulations
54
What is 21 CFR 3?
Definition of primary mode of action of a combination product
55
What is 21 CFR 50?
Protection of human subjects
| Informed consent
56
What is 21 CFR 56?
Institutional review boards
57
What is 21 CFR 58?
Good laboratory practice (GLP) for non-clinical lab studies
58
What is 21 CFR 314?
New drug applications
59
What is 21 CFR 601?
Biologics license applications regulations
60
What is 21 CFR 54?
Financial disclosures by clinical investigators
61
What is 21 CFR 25?
Environmental impact considerations
62
What is 21 CFR 201 and 202?
Labeling and advertising
63
What is 21 CFR 210 and 211?
Current good manufacturing practices (cGMP)
64
What is 21 CFR 807?
Establishment, registration, and device listing for manufacturers and initial importers of devices
65
What is 21 CFR 1270 and 1271?
Human tissues
66
What is a regulated environment?
Controlled environment where decisions made and operations performed are based a on predefined set of criteria
67
What are the program building blocks?
Chemistry, manufacturing, and controls (CMC)
Nonclinical/preclinical
Clinical (Protocol)
68
What is an IND?
Request for authorization from FDA to administer investigational drug or biologic to humans
Exemption to transport product across state lines for clinical investigation
69
When is an IND required?
When an approved drug/biologic is used in a clinical investigation
Clinical investigation is for approved drug but new indication
70
When is an IND not required?
Product is approved for medical practice
Investigation does not involve route of administration, dosage level, or use that significantly increases risk and conducted in accordance to IRB and informed consent requirements
71
What if a study is performed outside of the US with an IND?
Test article can be exported from US
| Study must conform to US IND regulations
72
What if a study is performed outside of the US without an IND?
May be accepted for FDA review in support of a marketing application
Export of the test articl from the US must conform to FDA regulations
73
What is a pre-IND meeting?
Meeting held with FDA before submission of IND
Intended to help ensure all documents are adequately prepared before submission
Not intended as a data review or negotiation meeting
74
T/F: having a pre-IND meeting does not guarantee safety from a clinical hold?
T
75
What is a clinical hold?
Legal order to delay or stop the study
76
What may lead to a clinical hold?
Exposure of subjects to unreasonable risk
Investigator brochure is misleading, erroneous or materially incomplete
Protocol design is inadequate or problematic
Investigator is not qualified
77
What are some regulatory filing strategies?
```
Accelerated approval
Fast-track/expedited review
Rolling/modular submission
Priority review
Special protocol assessment
```
78
What is accelerated approval?
Specializd program to enable promising therapies for serious or life-threatening conditions and that fill unmet medical need to reach the market faster
Contains "surrogate" endpoints or clinical endpoints that can be measured earlier than an effect on irreversible morbidity or mortality
79
What is fast track review?
Facilitates development and expedites review of drugs and biologics intended to treat serious or life-threatening conditions and demonstrates potential to address unmet medical needs
80
What are some special protocols?
Animal carcinogenicity
Final product stability
Phase 3 clinical trials that will form the primary basis for an efficacy claim
81
What is the biologics equivalent of a NDA?
Biologics license application (BLA)
82
What is the NDA approved by?
Federal food, drug, and cosmetic act (FDCnA)
83
What is the BLA approved by?
Public health service act (PHSA) and specific sections of the FDCnA
84
What is BIMO?
Bioresearch monitoring program
85
What is GLP and when was it established?
1979
Regulations addressed process not science of preclinical safety studies
Required good recordkeeping and collection of toxicological and pharmacological data
86
What is GCP?
Good clinical practice
International ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve human subjects
87
What are the GCP objectives?
Protect safety, well-being and privacy of human subjects
| Data integrity
88
What is 21 CFR 11?
Electronic records and signatures
89
What is 21 CFR 812?
Investigational device exemptions
90
What is 21 CFR 814?
Premarket approval of medical devices
91
What is the medical device equivalent of IND?
Investigational device exemptions (IDE)
92
What is ICH?
International conference on harmonization
93
What is the ICH guideline for GCP?
Provide unified standard for EU, Japan, and US to facilitate mutual acceptance of clinical data
94
What are the GCP practice tenets?
Rights, safety, and well-being of trial subjects should prevail over interest of science and society
Clinical RnD activities must be conducted within the context of an established plan
Clinical RnD tasks must be conducted according to written standardized procedures
Clinical RnD systems and procedures must be tested by conducting planned reviews and audits to ensure validity of data and compliance with applicable requirements
95
What is SOPs?
Standard operating procedures
| Standardization of terms and definitions, documentation, and research activities
96
What is quality control?
Operational techniques and activities within quality assurance system to verify that requirements for quality of trial-related activities have been fulfilled
97
What is quality assurance?
Planned and systematic actions established to ensure that the trial is performed and data is generated, documented, and reported in compliance with GCP and applicable regulatory requirements
98
What main categories make up ICH-GCP principles?
```
Ethics
Protocol and science
Responsibilities
Informed Consent
Data quality and integrity
Investigational products
Quality control and assurance
```
99
What does an investigator's brochure contain?
```
Description of investigational product
Rationale for research
Physical, chemical, and pharmaceutical properties and formulation
Non-clinical studies
Effects in humans
```
100
What is a clinical protocol?
Detailed step by step description of how the study must be conducted
101
What are the key components of a protocol?
Synopsis
Background info
Objectives
Subject selection and conditions for withdrawal
Treatment of subjects
method of subject assignment to treatment groups
Efficacy (drugs) or effectiveness (devices) and/or safety statements
102
What is an open trial design?
Investigator(s) and subjects are aware of the treatment assignment
103
What is a single-blinded trial design?
Only the investigator is aware of the treatment assignment
104
What is a double-blinded trial design?
Investigator(s) and subjects are unaware of treatment assignment
105
When is a "masked evaluator" used?
Device trials when it is not possible to mask treatment assignment from the subject and investigator(s)
106
Why is randomization used?
To minimize potential for bias
107
What is a parallel trial design?
Subjects are randomly assigned to participate in one arm of the study (i.e. treatment or control group)
108
What is a cross-over trial design?
Subjects are randomly assigned to participate in one arm of the study and then switched over to the other arm after a specified period.
109
What is a stratified trial design?
Subjects are statistically allocated to treatment arms based on characteristics that may affect the outcome of the study
110
What is a matching trial design?
Subjects are paired according to characteristics and then one is assigned to treatment and the other to control
111
What is a CRF?
Case report form or data collection form
Anything that needs to be entered into the database and analyzed to determine the study's endpoints and evaluation of safety
112
What is a PI?
Principal investigator
Lead investigator at the site who takes full responsibility for conduct of the trial and activities of his/her designated staff
113
What is a sub-investigator?
Qualified individuals who assume various for the medical/scientific conduct of the study as designated by the PI
114
What are some PI specific responsibilities?
Determining subject eligibility
AE, SAE/SADE, and UADrE/UADE assessment(s) and reporting
Keeping sponsor informed of IRB approvals
CRF sign-off
115
What is documentation?
All records that describe or record the methods, conduct, results, and factors affecting a trial, and the actions taken
116
What are source documents?
First hard copies on which clinical observations are recorded
Legally valid raw data that support a study's findings
117
What is a study coordinator?
Individual at the study site who is designated by the PI to assume various responsibilities for the daily conduct of the study
118
What are some study coordinator responsibilities?
```
Subject ID
Screening and enrollment
CRF completion
Maintenance of regulatory (essential) documents
Reporting AEs and deviations
Communicating with the IRB
```
119
How can an investigator get disqualified?
Beginning study without prior FDA/IRB approval
Ignoring dictates of IRB
Falsifying data
Failure to get informed consent and deceiving the patient
Deviating from the protocol or established procedures
Refusal of file audits
120
What is a sponsor?
Individual/company/governmental agency/academic institution/private organization who funds a study
121
What are some sponsor responsibilities?
```
Select qualified investigators
Monitor progress of trial and safety
Ensure protocol compliance
Drug disposition and reconciliation
Maintain required records and reports
Transfer of obligations to a CRO
```
122
What is study management?
Clinical/project manager responsible for the overall development, implementation, and management of the clinical trial to ensure compliance with Sponsor's responsibilities
123
What is a medical monitor?
Medical doctor responsible for assessment of AE and relationship to investigational product and interpretation of clinical study results
124
What is the purpose of monitoring?
Verify that rights and well beings of human subjects are protected, data integrity, and trial is conducted in accordance to currently approved protocol, GCP, applicable regulatory requirements and SOPs
