CRF 21 and CRF 45 Flashcards
(86 cards)
1
Q
What is included in exempt research?
A
- Educational practices
- Survey/test data that can’t be identified or cause harm if identified
- Benign behavioral intervention - can’t be identified or cause harm
- Secondary research in which consent is not required, or broad consent can be used, including storage and maintenance
- Public benefit or service programs
- Taste and food quality eval studies
2
Q
What is considered RESEARCH according to 45 CRF 46?
A
A systematic investigation designed to develop or contribute to generalizable knowledge
3
Q
What is a clinical trial?
A
A research study in which one or more human subjects are prospectively assigned to one or more interventions to evaluate the effects of the interventions
4
Q
What is an Intervention?
A
Physical procedures by which information or biospecimens are gathered and manipulation of the subject or subject’s environment for research purposes
5
Q
IRB’s should include…
A
- at least 5 members
- One scientific member and one non-scientific member
- One member not affiliated with institution
6
Q
Why would a continuing review not be required?
A
- Eligible for expedited or limited review
- In data analysis only
- Accessing follow-up data through normal clinical care
7
Q
Criteria for IRB approved research
A
- Risks are minimized
- Benefits outweigh risks
- Selection of subjects is equitable
- Informed consent will be sought and documented
- Data monitoring for safety
- Protect privacy/confidentiality
8
Q
How long should IRB records be retained according to part 50.
A
3 years after the completion of the research
9
Q
What are the basic elements of informed consent (there’s 9)?
A
- Statement of purpose, duration, and procedures
- Risks and discomforts
- benefits
- alternative procedures
- Confidentiality
- Compensation in case of injury
- Contact info
- Participation is voluntary
- Statement about collection and storage of identifiable info/specimens
10
Q
What does a broad consent include?
A
-A general description of research that may be conducted,
- identifiable info that might be used,
- period of time of storage,
- a statement that they will not be contacted for additional uses,
- a statement that results may not be disclosed, and contact info.
11
Q
Who should sign the protocol?
A
Sponsor and investigator
12
Q
What is an Adverse Drug Reaction?
A
An unwanted reaction to a drug (or normal dose) that is suspected to be related to the drug but unintended
13
Q
What form do investigators use if they have financial disclosures?
Disclosure : financial interest in arrangements of clinical investigators
A
3455
14
Q
What form do investigators use if they DO NOT have financial disclosures? Certification:
Financial interests in arrangements of clinical investigators.
A
3454
15
Q
What is a short form consent?
A
Attests that the elements of informed consent have been presented orally to either the participant or the participant’s legally authorized representative - used for non-English speaking subjects. IRB approves the summary.
16
Q
Who should sign a short form?
A
Subject or LAR signs the short form, the witness signs both the short form and the summary, and the person explaining consent signs the summary. Subject gets a copy of both.
17
Q
When is research with pregnant women allowed?
A
- There’s been previous research
- Benefit outweighs risk to both mother and fetus
- Direct benefit woman and /or fetus, or not greater than minimal risk
- When benefit is solely to fetus, father should sign consent
- Researchers do not have any part in decisions for termination or viability of neonate
18
Q
Who must sign the consent if research is done on a non-viable neonate or if there is only benefit to the fetus?
A
Both mother and father or their LAR. One can sign of other is unable. LARs can’t sign for nonviable neonates
19
Q
What are the IRB requirements for research with prisoners?
A
A majority of the board has no association with the prison.
At least one member is a prisoner or prisoner representative
20
Q
When is research with wards allowed?
A
- related to their statuses as wards
- Conducted in settings, where the majority of children involved are not wards.
- The IRB requires an appointment of an advocate reach that is not associated with the research
21
Q
What are IRB registration requirements including updates?
A
- Approved by OHRP.
- Registration must be renewed every three years.
- any changes must be updated within 90 days.
- Disbanding or discontinuation of IRB must be reported to OHRP in writing within 30 days
22
Q
What needs to happen if there’s an immediate use of a test article before IRB approval?
A
A physician who is not part of the investigation needs to review and evaluate the use, and be submitted to the IRB within five business days
23
Q
Who is responsible for approval of exception of informed consent for emergency research and how long do they have to retain records?
A
The IRB is responsible for reviewing, approving, and ensuring procedures are in place to get consent if possible.
3 years after completion of investigation
24
Q
What happens if an IRB cannot approve a clinical trial?
A
IRB must document and promptly provide findings in writing to the investigator and sponsor. The sponsor must then promptly inform the FDA and all other site investigators.
25
Research that involves more than minimal risk with children, must be:
1. Risk is justified by the anticipated benefits
2. Benefit to the child
3. Assent of child and permission of parent
4. Intervention will yield knowledge of vital importance
5. Sound ethical principles are followed
26
True or False: The FDA may restrict, suspend or terminate an IRBs use of expedited review when necessary to protect the welfare of subjects.
True
27
What should IRB records include?
1. Copies of all documents submitted by investigators
2. Minutes
3. Records of Continuing reviews
4. Correspondence with investigators
5. List of IRB members
6. Written procedures
7. Statements of significant new findings
28
What are the requirements for labeling an investigational new drug?
1. Must be labeled "Cautions: New Drug-Limited Federal law to investigational use"
2. Cannot bear any false or misleading statements (safety and efficacy)
29
What are the requirements if a sponsor wants to charge for an investigational drug?
1. Provide evidence of potential clinical benefit
2. Data to be obtained is essential to establish safety and efficacy
3. Demonstrate that trial could not happen without charging
30
What are the requirements for charging for expanded access (of an investigational drug)?
1. Assurance that charging will not interfere with developing drug for approval
2. Evidence the trial has sufficient enrollment, progress and milestones
3. Charge is limited to the # of patients authorized to receive drug
4. Access limited to 1 year from FDA auth - can request additional
31
Phase 1
Tests the safety, dosage range and side effects in a small # of people (20-80)
Also include studies on drug metabolism and the mechanism of action in humans
32
Phase 2
Tests the efficacy, safety, and optimal dosage of a new treatment in a larger group (100-300) with a specific disease/indication
33
Phase 3
Additional info on efficacy and safety (monitor adverse reactions) to evaluate the overall risk-benefit relationship (several hundred to several thousand volunteers)
34
IND Cover Sheet
-form 1571
-sponsor info, phase, IRB info, monitor info, CRO info, signature of sponsor
35
What needs to be included in an IND (paperwork - there’s 9)
1. Cover sheet (form 1571)
2. Table of Contents
3. Introductory statement and investigational plan
4. Investigators brochure
5. Protocol
6. Chemistry, manufacturing, and control information
7. Pharmacology and toxicology info
8. Previous human experience with drug
9. Additional info in certain cases
36
What needs to be in the Investigator's Brochure?
1. Description of drug and formulation
2. Pharmacological and toxicological effects
3. Pharmacokinetics
4. Info on safety and effectiveness in humans
5. Possible risks and side effects
37
IND protocols must include:
1. Objectives and purpose
2. Statement of qualifications of investigators
3. Criteria for patient selection
4. Study design
5. Method for determining dose
6. Observations and measurements
7. Clinical procedures and lab tests
38
Submission requirements for an IND
1. Must be in English
2. Need to submit original and 2 additional copies
3. Each submission should use a single, 3-digit serial number. Subsequent submissions are numbered in sequence
4. If exception to informed consent - state on cover sheet prominently that investigation is subject to 50.24
39
What is an adverse event?
Any untoward or unfavorable medical occurrence associated with the use of a drug. (related or unrelated)
40
What is a life-threatening adverse event (or suspected adverse reaction)?
Its occurrence places the patient at immediate risk of death
41
What is a serious adverse event (or suspected adverse reaction)?
An adverse event that results in death, a life-threatening adverse event, hospitalization (or prolonged), incapacity/disability, or a birth defect.
42
What is a suspected adverse reaction?
There is a reasonable possibility the drug caused the adverse event.
Implies a lesser degree of certainty about causality than an adverse reaction.
43
What is an unexpected adverse event (or unexpected suspected adverse reaction)?
If an adverse event is not listed in the IB, not listed in the specificity and severity, or not consistent with risk info. It also includes AEs listed in IB as occurring with a class of drugs, but not this drug.
Note: subject to expedited reporting until I is amended.
44
To whom and when should an IND safety report of potential serious risks be reported?
The sponsor must notify the FDA and all participating investigators no later than 15 days after sponsor determines it qualifies for reporting.
Unexpected fatal or life-threatening suspected adverse reaction (no later than 7 days)
45
What adverse events need to be reported to the FDA?
Both serious and unexpected.
Only report a suspected adverse reaction if there is evidence to suggest a causal relationship between event and drug.
Examples: Event is uncommon and strongly associated with drug exposure, uncommon with drug exposure but otherwise uncommon during drug exposure in normal population, analysis of events show events are more common in drug group than placebo.
46
How often do IND safety reports need to be submitted?
- Serious and unexpected adverse reactions (no later than 15 days)
- Annually, within 60 days of IND anniversary date
- New safety findings from research, increased rate of occurrence
-Unexpected fatal or life-threatening suspected adverse reaction (no
later than 7 days)
47
What form are **mandatory** IND safety reports submitted?
3500A
Must be transmitted to the the review division of the Center for Drug Evaluation and Research or the Center for Biologics Evaluation and Research
Additional requests by FDA must be submitted no more than 15 days after request
48
Unexpected fatal or life-threatening suspected adverse reaction reports must be submitted...(from the sponsor to the FDA)
ASAP, but no later than 7 days of sponsor's receipt of information
49
What should be included in the IND annual report?
1. Title, purpose, patient population, and study status
2. Expected N and # enrolled by demographics (completed and withdrawn)
3. Brief description of results (if available)
4. Summary information (frequent AE's and SAE's and body systems in a table, IND safety reports submitted past year, AE-related dropouts, deaths, new findings on safety)
5. Updated investigational plan for the year
6. Describe any changes to IB
7. Modifications to Phase 1 protocols not reported
8. Summary of foreign market developments
50
An IND goes into effect....
30 days after the FDA receives the IND, or earlier on FDA authorization
51
What is a clinical hold?
An order issued by the FDA to the sponsor to delay a proposed investigation or suspend an ongoing investigation
-May apply to one or more investigations covered by an IND
-Subjects may not be given drug, no new subjects recruited, patients enrolled should be taken off drug, unless permitted by FDA in the interest of patient safety.
52
What are some reasons for a clinical hold (Phase I, II, or III)?
- Subjects would be exposed to unreasonable and significant risk of
injury
- PIs not qualified
- IB is misleading, erroneous, or incomplete
- not enough info to assess risks
- excluding one gender due to risk of reproductive/developmental toxicity
53
What are some reasons a phase II or III would be terminated?
- Safety, method, reporting, and truthfulness issues, IND inactive for 5
years
- The scientific plan/protocol won't reasonably determine whether
drug is safe and effective
- There is convincing evidence the drug is not effective
54
If a study is terminated by the FDA and the sponsor responds but the FDA does not accept the response, how many days does a sponsor have to request an FDA regulatory hearing?
10 days
55
Why would an IND be given inactive status by the FDA?
- No subjects enrolled in 2 years or more
- On a clinical hold for 1 year or more
- Remains on inactive status for 5 years or more
56
What is and what is included in form 1572?
Signed investigator statement
- Name and address of PI, facility, labs used, IRB
- Names of sub-investigators
- Name and code of any protocols in IND
- Commitment by investigator
57
What info does the sponsor need to get from each investigator before starting the study?
1. From 1572 - Signed investigator statement
2. Investigator CV
3. Clinical Protocol
4. Financial disclosures (3454 or 3455)
58
How many days does the sponsor have to discontinue investigations if they determine the drug presents an unreasonable or significant risk?
No later than 5 working days
59
How long does a sponsor and investigator need to retain records after drug market approval?
2 years
If no market approval - 2 years from discontinuation of drug
60
What devices are exempt from an IDE?
is noninvasive; does not require an invasive sampling procedure that presents significant risk; does not by design or intention introduce energy into a subject;
61
What is a supplement application for an IDE?
An investigational device (IDE) supplement is a request from a sponsor to the FDA for approval of changes to an approved IDE. The FDA tracks these requests as supplements. Some examples of IDE supplements include:
Changes to the device design or manufacturing
Changes to the approved protocol
Changes to informed consent
Requests for approval of additional clinical study sites
5-day notices that changes have been made that don't require prior FDA approval
Requests for compassionate use or live case demonstrations
62
How often do treatment IDEs need to be reviewed?
Semi-annually
63
How long after the completion of an investigation does an investigator need to report financial disclosures?
Promptly and 1 year after completion of the study
64
Unanticipated adverse device effects requirements
1. Sponsor must immediately evaluate
2. If unreasonably risk to subjects, investigation must be terminated with 5 working days and no later than 15 working days after the year first received notice
65
How long does an investigator or sponsor have to notify FDA of a transfer of responsibility to maintain records?
10 working days
66
Under no circumstances can investigator permit authorized FDA employees to inspect records of identified subjects.
False
They can if the FDA suspects ICF was not obtained or investigator submitted records are incomplete false or, misleading
67
When do unanticipated adverse device effects need to be reported into who?
The investigator shall submit to the sponsor and IRB asap to no later than 10 working days
68
In what time frame does an investigator need to submit a final report to the Sponsor and IRB??
Within 3 months
69
How often does the Sponsor need to submit a current list of investigators to the FDA??
Every 6 months
70
In what time frame does a sponsor need to notify and then produce a final report?
The sponsor shall notify the FDA within 30 working days of the completion or termination.
Final report to FDA in all reviewing IRB‘s and investigators within six months .
71
What is an independent data-monitoring committee (IDMC)?
Or DSMB
-Assesses trial progress and recommends continuing, modifying, or stopping a trial.
-Composed of experts in their fields that are independent from the Sponsor of the trial
72
What is direct access?
Permission to examine, analyze, verify and reproduce any records or reports from a clinical trial
73
Besides ADRs, what are some examples of other observations that should be reported immediately?
-an increase raise of expected serious ADR
-Significant hazard to patient population
-major safety finding from animal study 
74
When should fatal or life-threatening unexpected adverse drug reactions be reported according to ICH?
No later than 7 calendar days after first knowledge followed by complete report within 8 additional calendar days.
75
When should all other serious unexpected ADRs be reported according to ICH?
ASAP or no later than 15 calendar days after first knowledge 
76
What is the minimum criteria for reporting ADRs according to ICH? (What do you need?)
1. Identifiable patient,
2. Asuspected medicinal product
3. identifiable reporting source
4. event that can be identified as serious and unexpected and there is a reasonable suspected casual relationship.
77
How does the ICH recommend managing serious ADR‘s in blinded studies?
The blind should be broken only for that patient by the Sponsor, even if the investigator has not broken the blind. Those responsible for analysis and interpretation of results should remain blinded.
78
What is form FDA 482?
Notice of inspection
79
What is form FDA 483?
Inspectional observations
80
What form are ** voluntary **IND safety reports submitted?
Form FDA 3500
81
What is a 510(k) clearance?
Premarket notification - notify FDA intent to market a medical device at least 90 days in advance
82
What is a Humanitarian Use Device?
A device that is intended to benefit patients affecting not more than 8,000 individuals in the US per year.
83
According to OHRP, unanticipated problems should be reported if they are….
Unexpected
Related
Greater risk of harm
84
When is an IND needed?
1. New drug (chemical)
2. New indication
3. New dosage form
4. New dosage level
5. New drug combination
85
Requirements of importing a drug?
Consignee in US is sponsor of IND
Consignee is qualified investigator
Consignee is responsible for the control and distribution of the drug
86
Requirements for exporting investigational new drug?
Drug complies with laws of the country it’s being exported
Consignee is qualified investigator
Need approval from FDA
