Study Guide Flashcards
(125 cards)
1
Q
What are the basic elements of informed consent? (8)
A
- A statement that the study involves research and the purpose, duration and procedures to be done and identification of any procures which are experimental
- Any reasonable foreseeable risks or discomforts
- A description of any benefits
- A disclosure of appropriate alternative procedures
- A statement describing how the confidentiality or records will be maintained (possibility for the FDA to review records)
- For research involving more than minimal risk, an explanation as to whether any compensation or medical treatments are available in injury occurs
- Who to contact for questions about the research or who to contact in the event of research related injury
- Participation is voluntary and subject may discontinue at anytime
2
Q
Are applicable clinical trials required to have a statement in their consent regarding ‘clinicaltrials.gov’?
A
Yes. The specific statement is “A description of this clinical trial will be available on ‘clinicaltrials.gov’ as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time”
3
Q
Can the sponsor provide sample consent forms?
A
Yes. Although IRBs often have their own standard language.
4
Q
Who has the final say to approve/disapprove consent forms
A
IRB
5
Q
A short form
A
A document that states the elements of informed consent have been presented orally to and understood by the participant (or their LAR)
6
Q
A written summary
A
The written oral summary of what is to be said to the participant and LAR which is IRB approved
7
Q
Who signs the short form?
A
The subject (or LAR) and the witness
8
Q
Who signs the written summary?
A
The consenter and the witness
9
Q
What situations may an investigator use short form consent document?
A
- When a potential subject does not understand English and the investigator does not have an IRB-approved consent document translated into appropriate language
- When the window of opportunity for a subject to benefit from research participation is brief, and the IRB finds that by use of short form consent document is appropriate
10
Q
Informed consent serves as a proof of the subjects _______________ in a clinical trial.
A
authorization to participate
11
Q
When reviewing the informed consents a CRC or clinical research associate (CRA) should ensure
A
- The subject signed the most recent IRB approved version
- The subject signature is present in addition to the subject’s name
- The subject dated for themselves and the date is correct (verify against date of visit and date/time of study procedures on medical records)
- An error was corrected by drawing a single line through the error
- All pages of the informed consent document are present
12
Q
What is source data verification (SDV)?
A
The process where data within the case report form (CRF) or other data collection systems are compared to the original source of information to confirm data accuracy
13
Q
What is source data review (SDR)?
A
A review of source documentation to check quality, review protocol compliance and ensure compliance
14
Q
What are case report forms (CRFs)?
A
A paper or electronic document designed to record all of the protocol required information to be reported to the sponsor.
15
Q
What should one consider when reviewing/verifying information on a CRF?
A
- Compare the data recorded on the CRF against the data from the source documents
- Where source data was entered directly into the CRF, the signature (or initials) of the person recording and date should be present
- Additional - matches what is specified in the protocol
16
Q
What adverse events need to be documented and where?
A
All adverse events (unrelated or related to the study) need to be documented in the AE page of the CRF and the patient’s medical records
17
Q
What should be considered when reviewing/verifying AEs on the CRF
A
- Ensure all AEs are recorded on both the CRF and in the patient’s medical chart
- Ensure proper protocol procedures were followed for AEs
- Check that responsible person (investigator or designee) assessed AEs for seriousness, causality, and expectedness
18
Q
Per CRF 312 when should investigators report SAEs, to who and what should be included in report?
A
Immediately - To sponsor
Promptly - To IRB
An assessment of whether there is a reasonable possibility that the drug caused the event
19
Q
Per CRF 312 when should sponsors report SAEs, to who, under what circumstances?
A
ASAP, but no later than 15 calendar days
To the FDA and all participating investigators
After the sponsor determines that the information qualifies for reporting as:
1. Serious and unexpected suspected adverse reaction (i.e., SAEs)
2. Findings from other studies (e.g., pooled analysis of multiple studies)
3. Findings from animal or in-vitro testing (e.g., reports of organ toxicity near the expected human exposure)
4. Increased rate of occurrence of serious suspected adverse reactions
20
Q
What is an unanticipated adverse device effect (UADE)?
A
- Any serious adverse effect on health or safety
- Life-threatening problem or death (caused by or associated with device)
- If that effect, problem or death was not previously identified in nature, severity, or degree of incidence in the application
- Any other unanticipated serious problems associated with a device that relates to the rights, safety or welfare of subjects
21
Q
Per CRF 812 when should investigators report UADE and to who?
A
ASAP, but no later than 10 working days after learning of effects
To the sponsor and IRB
22
Q
Per CRF 812 when should sponsors report UADE and to who?
A
10 working days
FDA and to all reviewing IRB’s and participating investigators
23
Q
45 CRF 46 Part A pertains to:
A
Informed consent/common rule
24
Q
45 CRF 46 Part B pertains to:
A
Pregnant women
25
45 CRF 46 Part C pertains to:
Prisoners
26
45 CRF 46 Part D pertains to:
Children
27
Consent needs to be obtained from the pregnant woman and father if...
If research may only benefit the fetus
*Not necessary from father if unable to obtain father's consent for appropriate reasons
28
What are the reasons a father's consent wouldn't need to be obtained
1. Unavailability
2. Incompetence
3. Temporary incapacity
4. Pregnancy resulted from rape or incest
29
Can research offer to terminate a pregnancy?
No. No inducements, monetary or otherwise will be offered to terminate a pregnancy. Individuals engaged in research will have no part in any decision as to the timing, method or procedures used to terminate a pregnancy or determining the viability of neonate.
30
True or False: Federal regulations require IRBs to classify research involving children into one of four categories?
True
31
What are the IRB classifications for research involving children?
1. Research not involving greater than minimal risk
2. Research involving greater than minimal risk (direct benefit)
3. Research involving greater than minimal risk (no direct benefit)
4. Research that is not otherwise approvable, but presents an opportunity to understand, prevent or alleviate a serious problem affecting the health or welfare of children.
32
How is consent for minors determined?
The overseeing IRB will determine whether informed consent from one or both parents is needed based on the risk to subjects (children/minors) involved. Additionally, the asssent of the child may be required.
33
What should the IRB consider when determining assentment requirements?
1. Nature of the research
2. Child's age, status and condition
3. Whether all or some of the children are capable of assenting to participate
34
What happens if a child reaches the legal age of consent while enrolled in a study?
The child should be re-consented for ongoing continuation in research unless the IRB determines that the requirements for obtaining informed consent can be waived
35
What is an additional federal protection for wards of the state when research involves greater than minimal risk with no direct benefit to subjects?
The research must be either related to the children status as wards or be conducted in settings where majority of children involved are not wards
36
Wards of the state must be appointed
An advocate
37
True or False: In general 18 years of age is the legal age of adulthood, but this can vary from state to state
True
38
Four examples of disclosable financial interests in arrangements
1. Significant payments of other sorts 25,000+ from the sponsor to the investigator or institution
2. Any stock that exceeds 50,000 during the time or the study and up to one year afterwards
3. Any equity interests (e.g., stocks) in any sponsor of the clinical trial
4. Proprietary interest in the tested product (e.g., patent, trademark, copyright)
39
When is financial disclosure for an investigator required?
During the course of the study (agreement with sponsor) and for one year after completion of the study (all subjects have been rolled and follow-up of primary endpoint data is completed)
40
What are the three primary responsibilities of an investigator?
1. Oversee the conduct of the trial under appropriate regulations
2. Protect the rights, safety, and welfare of subjects
3. Control the use of investigational product
41
What does Form 1572 state?
1. Conduct study according to the current protocol
2. Personally conduct or supervise the studies
3. Obtain informed consent
4. Report adverse event (AE)
5. Properly train staff and employees
6. Maintain adequate and accurate records
7. Ensure that an IRB complies with federal regulation and oversees the study
8. Comply with all other requirements CRF 312
42
What investigator form is used for IND?
Statement of Investigator Form (form 1572)
43
What investigator form is used for IDE?
Investigator Agreement not 1572
44
Form 1572 is a declaration of the ______ to comply with _______
Investigator
FDA regulations
45
Per FDA regulations, when do non-serious AEs need to be reported by the investigator?
No specific dateline for FDA. They should be recorded and reported to the sponsor following the description in the protocol.
46
True or False: The FDA does not provide specific dateline (e.g., number of days) for investigators in reporting SAEs
True. They only state "immediately" when reporting to the sponsor and "promptly" when reporting to the IRB
47
Per Federal Regulations, how long do investigators have to report serious adverse events to the sponsor and to the IRB?
No specific dateline for IND SAE for investigators. They should be reported "immediately" to the sponsor and "promptly" to the IRB.
48
True of False: The FDA does not provide specific dateline (e.g., number of days) for investigators in reporting unanticipated adverse device effects
False. The investigator should report the UADE to the sponsor and IRB ASAP but no later than 10 working days.
49
Per Federal Regulations, how long do investigators have to report unanticipated adverse device effects to the sponsor and to the IRB?
ASAP but no later than 10 working days to the sponsor and IRB
50
Do federal regulations limit who has access to an investigational product?
Yes. Regulations require an investigator to limit access to investigational products to only usage under the trial.
51
Does the FDA consider medical records to be an original document?
Yes. According to the FDA medical records are considered case histories and thus original documents.
52
Examples of Source Documents (as defined by ICH GCP)
Hospital records
Subjects' diaries
Evaluation checklists
Recorded data from automated instruments
Pharmacy dispensing records
Photographic negatives
X-rays
Records kept on site involved in the clinical trial
53
What does ALCOA-C stand for?
Attributable
Legible
Contemporaneous
Original
Complete
54
When can case report forms (CRFs) be considered source documents?
If the first recording of information was done on CRFs. Additionally, must be signed (or initialed) and dated by the person recording the information.
55
What should be documented for a subjects discontinuation?
1. Source - e.g., investigator withdrawn or subject self-withdrew
2. Reason (for discontinuation/withdrawal)
3. Impact - withdrawn from all components or just the primary interventional component?
56
List all the reports an Investigator must provide
1. Progress report (e.g., annual report/continuing review)
2. Safety report (e.g., AEs or SAEs)
3. Protocol deviation (date, reason)
4. Financial disclosure report (during the study and up to one year afterwards)
5. Final report
57
An investigator should keep documents for 2 years after (hint: two situations)
1. FDA approval of the marketing application
2. The study ends
58
What are the responsibilities of a sponsor? (hint: 6)
1. Selecting qualified investigators
2. Providing the information and training the investigators need to conduct an investigation properly
3. Ensuring proper monitoring of the investigation
4. Ensuring that the investigaton is conducted following the general investigational plan and protocols contained in the IND
5. Maintaining an effective IND
6. Promptly informing the FDA of significant new adverse effects or risks
59
What does the sponsor need prior to starting a clinical trial
1. Statement of Investigator
2. CV
3. Clinical protocol
4. Financial disclosure
60
What does the IB contain
1. Description of the drug substance and the formulation
2. The pharmacological and toxicological effects of the drug in animals (and humans if known)
3. The pharmacokinetics and biological disposition of the drug in animals (and humans if known)
4. Information on safety and effectiveness in humans obtains from prior clinical studies
5. Possible risks and side effects to be anticipated on the basis of prior experience with the drug under investigation or with related drugs, and of precautions of special monitoring to be done as part of the investigational use of the drug
61
Who must select a monitor to oversee clinical trials? Monitors are selected on wait bases?
Sponsors; based on training and experience (qualified monitor)
62
What happens if the sponsor determined the IND presents an unreasonable and significant risk to participants?
ASAP but no later than 5 working days the sponsor should notify the FDA, and all participating IRBs/investigators that they are discontinuing. Assure the disposition of the investigative drug, and submit a full report to the FDA.
63
What is an IND Safety Report? Who is it submitted by/to? When does it need to be submitted?
A report for any potential serious risk associated with the investigational product.
Submitted by the sponsor to the FDA and any participating investigators.
ASAP but no more than 15 calendar days after the sponsor determined the events meets reporting criteria.
64
What is the sponsor’s reporting criteria for an IND Safety Report?
1. Serious and unexpected suspected adverse reaction (SUSAR)
2. Findings from other studies
3. Findings from animal or in-vitro testing
4. Increased rate of occurrence of serious suspected adverse reactions
65
If the FDA request additional information for a Safety Report how long does the sponsor have to supply this information?
It should be submitted ASAP but no later than 15 calendar days after receiving the request
66
Examples of SUSAR
SUSAR = serious and unexpected suspected adverse reaction
1. A single occurrence that is uncommon and strongly associated with drug exposure
2. One or more occurrences of an event that is not commonly associated with drug exposure, but is otherwise uncommon in the population exposed to the drug
3. An aggregate analysis of specific events observed in a clinical trial (e.g., known consequences of the underlying disease or events that commonly occur in the study population independent of drug therapy) that indicates those events occur more frequently in the drug treatment group than in a concurrent or historical control group)
67
Per Federal Regulations, how long does the sponsor have to notify the FDA (and all participating IRBs/investigators) of unexpected fatal or life-threatening adverse reactions? Initial report only.
ASAP but no later than 7 calendar days after the sponsor's initial receipt of the information
68
Per Federal Regulations, how long does the sponsor have to notify the FDA (and all participating IRBs/investigators) of unanticipated adverse device effects?
Within 10 working days after the sponsor first receives notice of the effect
69
Per Federal Regulations, how long does the sponsor have to notify the FDA (and all participating IRBs/investigators) of withdrawal of IRB approval?
Within 5 working days after receipt of the withdrawal of approval
70
Per Federal Regulations, how long does the sponsor have to notify all participating IRBs/investigators of withdrawal of FDA approval?
Within 5 working days after receipt of the withdrawal of approval
71
Per Federal Regulations, how long does the sponsor have to notify the FDA (and all participating IRBs/investigators) of withdrawal of recall of device disposition?
Within 30 working days after the request is made and shall state why the request was made
72
Per Federal Regulations, how long does the sponsor have to notify the FDA (and all participating IRBs/investigators) of significant risk device determinations (e.g., considered significant risk by IRB when not submitted this way)?
Within 5 working days after the sponsor first learns of the IRBs determination
73
Per Federal Regulations, how long does the sponsor have to submit an annual report for an IND?
Within 60 calendar days of the anniversary date the IND went into effect
74
Per Federal Regulations, what are the sponsor's reporting requirements for an IDE that is not significant risk?
Annual report to the IRB
75
Per Federal Regulations, what are the sponsor's reporting requirements for an IDE that is significant risk?
Annual report to the IRB and FDA
76
Per Federal Regulations, what are the sponsor's reporting requirements for a treatment medical device?
Semi-annual (6-months) progress reports and annual reports to IRB and FDA
77
Per Federal Regulations, how long does the sponsor have to notify the FDA (and all participating IRBs/investigators) of completion or termination of the investigation of a significant risk device clinical trial?
Within 30 working days
78
True or False: Federal regulations require that the sponsor notify the FDA (and all participating IRBs/investigators) of completion or termination for a non-significant risk device within 30 working days.
False. Sponsors are only required to notify completion/termination for significant risk devices.
79
Per Federal Regulations, how long does the sponsor have to submit a final report for any medical device trial? Who is it submitted to?
Within 6-months after completion or termination; FDA and all participating IRBs/investigators
80
What are the four different types of IND?
1. Commercial IND - for a sponsor
2. Investigator IND - for a sponsor-investigator
3. Emergency Use IND - for the use of an investigational drug or biologic in an emergency situation that does not allow time for submission on an IND in a normal route
4. Treatment IND - for an investigational drug or biologic that show promise in clinical testing for serious or immediately life-threatening conditions while the final clinical testing and FDA review are taking place
81
What happens after an IND is submitted
There is a 30 calendar day hold for the FDA to review the IND for safety. The sponsor may initiate the clinical trial after 30 calendar days AS LONG AS IRB APPROVED and no notice from FDA regarding clinical hold
82
A sponsor should keep IND documents for 2 years after (hint: two situations)
1. After approval
2. After the last shipment and delivery of the investigational product and FDA was notified
83
A sponsor should keep IDE documents for 2 years after (hint: two situations)
1. After study termination or completion
2. After the date that the records are no longer required for a PMA or after the date on the notice of completion of protocol's requirements
84
What is done during pre-clinical testing (phase 0)
First phase of human testing (very small N = 10 to 15)
Phamacokinetics (PK) - understand what the body does to the drug
Pharmacodynamics (PD) - understand what the drug does to the body
Sometimes described as a part of phase I
85
Describe Phase I studies
The goal is to learn about the safety of the new drug
Small number of health subjects**
N = 20 - 80
Conducted in special facilities (e.g., CPUs) to monitor patients
Look at dose toxicity (e.g., max dose)
**exception for oncology trials where actual patients with disease may be used
86
Describe Phase II studies
The goal is to learn about efficacy of the new drug and imminent safety risks
Larger number of subjects, used in patients with the disease the drug is intended to treat
N = 100 - 300
Often hospitalized
Compares the new drug to standard care and/or placebo
Looks at dosing regiment
1 to 3 years to complete
87
Describe Phase III studies
The goal is to learn about long term safety and efficacy
Hundreds to thousands of subjects with the disease
Often referred to as a "Pivotal Study"
Upon favorable results the sponsor may submit a New Drug Application (NDA) to the FDA
2 to 5 years to complete
88
Describe Phase IV studies
Conducted after the approval of the new drug
The goal is to collect safety information in larger population (e.g., general population) over longer time (e.g., multiple years)
89
Grounds for clinical holds on Phase I studies:
1. Unreasonable risk
2. Unqualified investigators
3. IB is misleading, inaccurate or incomplete
4. IND doesn’t contain sufficient information to assess risk to subjects
90
Grounds for clinical holds on Phase II or III studies:
Protocol doesn't have enough information to meet stated objectives
91
When an ongoing study is on a clinical hold can new subjects be enrolled and what happens to subjects currently enrolled and on IP?
No new subjects,
Subjects on IP have to stop unless specifically permitted by the FDA
92
Who can appeal the FDA’s decision for a clinical hold?
Sponsor
93
Under an IND, if no subjects are entered into a study for 2+ years or if all studies under an IND remain on clinical hold for 1 year+, the IND may be placed on “_____”
Inactive Status
94
INDs that are "inactive" for ______ may be terminated
5 years
95
For an IND, when do Investigator’s provide annual report to sponsor?
No time criteria - submit to sponsor to submit to FDA
96
For an IND, when does the Investigator need to submit the final report to the sponsor?
When the study site is finished with the investigation (no specified time constraints)
97
For emergency use of a drug, where immediate use of the product was required and the patient was not able to be consented, how long does the sponsor have to notify the FDA of the use of the product?
5 working days
98
When is unblinding inappropriate in the case of a fatal or serious adverse event?
If a fatal or serious outcome is the primary efficacy endpoint, the integrity of the clinical investigation may be compromised if the blind is broken. It may be advantageous to reach an agreement with regulatory authority not to unblind and expedite reporting.
99
What is considered a significant risk device?
1. Implant and presents a potential for serious risk to the health, safety or welfare of a subject
2. Is purported or used for supporting or sustaining human life
3. Is used in diagnosing, curing, mitigating or treating disease or otherwise preventing impairment of human health and presents a potential for serious risk to
4. Otherwise presents a potential risk
100
Who makes the initial decision regarding medical device risk level? Explain what occurs for differing opinions for NSR.
Sponsor
IRB needs to agree to NSR, if not then goes to FDA to determine.
101
True or False non-significant risk (NSR) studies are required have an IDE application approved by the FDA prior to the study starting
False. Only significant risk (SR) studies are required to have an IDE application approved by the FDA prior to starting.
102
The sponsors request for a regulatory hearing must be made within ___ of the sponsors receipt of FDA’s notification of nonacceptance
10 calendar days
103
True or False. Non-significant risk device studies are exempt from IDEs?
False. Only exempt studies are expect from an IDE. Both SR and NSR require IDEs.
104
For non-significant risk IDEs, does the sponsor need to send a final report to FDA? How long after finishing a trial?
No, only to the IRB and within 6 months of finishing the trial.
105
For IDE, when and to who does the investigator have to submit a final report after finishing a clinical trial?
Investigator submits a final report to the Sponsor AND to the IRB within 3 months of finishing the trial.
106
True or False. If an IRB gives a decision of disapproval, the investigator has an opportunity to respond in person or in writing?
True. Within 15 (calendar?) days
107
What are the general characteristics of IRB submissions that qualify for expedited review?
They are no more than minimal risk or contain minor changes in previously approved research (of one year or less)
108
Under expedited review, how many IRB members are required in order to approve the research? What about disapprove the research?
Only one member is required to approve the research. However, if the member disapproves it must go through full IRB review in order to be disapproved or require changes.
109
All sponsor reporting time frame for ADRs (fatal or life-threatening)?
7 calendar days after first knowledge by sponsor that case qualified, followed by complete as possible report within 8 additional calendar days
110
Sponsor reporting time frame for ADRs (not fatal or life-threatening)
15 calendar days after first knowledge by sponsor that case meets minimum criteria for expedited reporting
111
If an investigator uses the test article in an emergency use situation, what must happen afterwards and in what time frame?
The investigator must have an independent physician review the reason for use within 5 working days of use. This documentation must be submitted to IRB within 5 working days of use.
112
Who created the Belmont Report?
the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research
113
What are the three applications of the Belmont Report
1. Informed Consent
2. Assessment of Risk and Benefits
3. Selection of Subjects
114
What are the three basic ethical principles of the Belmont report?
1. Respect for persons
2. Beneficence
3. Justice
115
Respect for persons = _________
Autonomy (informed consent)
116
Beneficence = _________
Do no harm (maximize benefits and minimize harm)
117
Justice = _________
Selection of subjects
118
Who created the Declaration of Helsinki
The World Medical Association
119
What is required for exception to informed consent for emergency research?
1. The human subject is in a life threatening situation
2. Obtaining informed consent is not feasible
3. Participation in the research holds a prospect of direct benefit to the subject
4. The research could not be carried out without the waiver
5. It is not possible to contact the LAR within the predefined potential therapeutic window and the investigator summarizes efforts made to contact LAR
6. IRB Approval
7. Additional protections have been provided
120
What is required for an IRB to waive informed consent? (non-emergency)
1. Research involves no more than minimal risk
2. Waiver will not adversely affect the rights and welfare of subjects
3. Research could not be carried out without the waiver
4. Subjects will be provided with additional pertinent information after participation
121
If a trial that uses children is greater than minimal risk and presents the prospect of direct benefit, what characteristics of the trial are required for IRB approval?
1. Risk is justified by the benefits
2. Benefit is is similar to those presented by available alternatives
3. Adequate provisions made for getting assent/consent
122
If a trial that uses children is greater than minimal risk without the prospect of direct benefit, what characteristics of the trial are required for IRB approval?
1. Risk is little more than minimal risk
2. Intervention / procedure is similar in proportion / likelihood to what they would experience with standard of care
3. Intervention / procedure is likely to yield generalizable knowledge about the condition
4. Adequate provisions in place for assent / consent
123
How is the prospect of direct benefit to the subject determined?
1. Subject is facing life-threatening situation that necessitates intervention
2. Appropriate animal and other preclinical studies have been conducted, supporting potential for direct benefit
3. Risks associated with investigation are reasonable in relation to what is known about medical condition of potential class of subjects, and risks/benefits of standard therapy, and what is known about risks and benefits of proposed intervention or activity
124
Criteria for IRB approval of clinical trial
1. Risks to subjects are minimized.
2. Risks to subjects are reasonable in relation to anticipated benefits.
3. Selection of subjects is equitable.
4. Documented informed consent for each subject
5. Research plan makes adequate provision for monitoring the data collected.
6. Adequate provisions to protect the privacy of subjects and to maintain confidentiality of subjects.
125
Reporting timeframes for the IRB
90 days if changing contact person
30 days if disbanding
At the time of renewal (every 3 years) if other
