Practice Questions Flashcards
1
Q
What would be the first priority for an investigator when a subject wishes to withdraw prematurely from the trial?
A
Try to obtain the subjects reason for withdrawal
2
Q
A CRO recently switched from paper CRF to an EDC system. The EDC system must conform to the established requirements for:
A
Validation, accuracy, reliability, completeness
3
Q
Part of a sponsor’s responsibility pertaining to electronic trial data handling is to…
A
Maintain an audit trail, data trail, and edit trail
4
Q
A research subject’s responsibilities for study participation should be described in the…
A
ICF
5
Q
What document would an investigator reference to learn more about the previous clinical and nonclinical results of studies of the IP?
A
Investigators brochure
6
Q
During a multi site clinical study, whose responsibility is it to report subject recruitment rate?
A
CRA
7
Q
An unconscious adult subject was enrolled in a study after obtaining consent from an LAR, and protocol therapy was initiated. The subject showed significant improvement in his clinical condition, and regained consciousness. The Investigator should inform the subject about the study and…
A
Obtain consent from the subject for the study
8
Q
A site is in the start up phase of an industry sponsored phase 3 trial, and has received IRB approval. The site can begin enrolling subjects after…
A
A signed clinical trial agreement between the site and sponsor is in place
9
Q
A site is screening potential subjects for a study looking at mild cognitive impairment. One of the inclusion criteria is a score of 25 or less on a psychometric test, a research specific tool which measures cognitive ability. Which of the following individuals can administer the psychometric test to the potential subjects?
A
A research assistant who is certified to administer the psychometric test
10
Q
A research study, in which there is no intended clinical benefit to the subject, is being submitted to the IRB. What benefit information should be included in the ICF?
A
Wording indicating that there is no expected benefit should be included
11
Q
A CRA notices during an onsite visit that the date on IRB approval letter for a protocol is prior to the effective date indicated on the cover page of the protocol and the signatures of the investigator and sponsor. What should the CRA do first?
A
Confirm dates of initial receipt of the sponsor protocol and the IRB submission dates.
12
Q
In a multi arm, randomized clinical trial, one arm of the protocol was terminated due to an increased risk of cancer in subjects. Who is responsible for providing a written report to the IRB?
A
PI
13
Q
Prior to archiving a study, documentation of IP destruction at the site should be filed in the study files of the…
A
PI and Sponsor
14
Q
During a monitoring visit, what records would a CRA reference to verify a subject’s compliance to the study visit schedule and assessments?
A
Electronic medical record
15
Q
New safety information has become available from the Sponsor about the IP being used in a clinical trial. The investigator must…
A
Submit a revised ICF to the IRB noting the new safety information
16
Q
Per ICH, an IRB must keep correspondence for at least how long after the completion of a clinical trial?
A
3 years
17
Q
Why would an impartial witness be needed during the consent process for an illiterate subject?
A
To observe the consent process
18
Q
A study which seeks to determine the ideal dose and regimen of a new IP to treat hypothyroidism is considered to be what phase?
A
Phase II
19
Q
After completion of a study, the final trial close out monitoring report prepared by the CRA should be filed in which of the following stakeholder files?
A
Sponsors
20
Q
A blood sample collection is required to screen for bloodborne pathogens before subject could be enrolled in a study. Where will subjects find information of the procedures and any foreseeable risks or inconveniences?
A
ICF
21
Q
When should a research study involving human subjects be registered in a publicly accessible database?
A
Before recruiting the first subject
22
Q
In the case of an incapacitated subject, who should receive a copy of the signed and dated ICF?
A
The subjects legally acceptable representative
23
Q
A medical student is approached by a faculty member for possible participation in cricothyroidotomy simulation research study. Which of the following increases risk to the study?
A
Consenting in the presence of figure of authority
24
Q
The clinical trial phase that focuses on safety and human pharmacology in healthy volunteers.
A
Phase I
25
Who is ultimately responsible for all aspects of the research conducted at a site?
PI
26
Define GCP
An international quality standard that is provided by ICH E6(2) describing safety, accuracy of trials and credibility of data
27
What event resulted in the Nuremburg Cod of 1949?
Nazi Medical Experiments
28
Which signatures are required by ICH Guidelines to be on the Informed Consent Form (ICF)?
a. The investigator
b. The person who conducted the informed consent discussion
c. The investigator and the subject
d. The subject
The person who conducted the informed consent discussion & the subject
29
Whose responsibility is it to safeguard the rights and safety of subjects in clinical trials? (Select all that apply)
a. The investigator
b. The sponsor
c. The IRB/IEC
d. The subjects' general practitioner(GP)
The investigator, The sponsor & The IRB/IEC
30
Which hospital personnel are normally directly involved in a clinical trial? (Select all that apply)
a. Research nurses
b. The sponsor
c. Pharmacists
d. Hospital orderlies
Research nurses, Pharmacists
31
Who does the investigator need to inform if he/she deviates from the protocol? (Select all that apply)
a. The sponsor
b. The regulatory authorities
c. The office staff
d. The IRB/IEC
The sponsor, The regulatory authorities, The IRB/IEC
32
Who should have access to the trial files? (Select all that apply)
a. The subiect
b. The monitor
c. The investigator
d. The pharmacist
The monitor, The investigator
33
An Adverse Event (AE) that is severe in intensity:
a. Is always classified as serious
b. Is never classified as serious
c. May not meet the definition of serious
d. Should be submitted to the sponsor within 24 hours
May not meet the definition of serious
34
Which of the following is always true?
a. Adverse Drug Reactions (ADRs) are evidence that the drug is working
b. An Adverse Drug Reaction (ADR) is an Adverse Event (AE)
c. An Adverse Event (AE) is an Adverse Drug Reaction (ADR)
d. Adverse Events (AEs) are less frequently observed in placebo arms.
An Adverse Drug Reaction (ADR) is an Adverse Event (AE)
35
Which of the following tasks is the investigator responsible for? (Select all that apply)
a. Treating the subject if an Adverse Event (A) occurs in the case the investigator is a qualified physician or dentist
b. Make reasonable efforts to ascertain the reasons for a subject's premature withdrawal from the trial
c. Encouraging subjects to report all Adverse Events (AEs)
d. Upon permission of the subject, inform primary physician of subject's participation in the trial
a. Treating the subject if an Adverse Event (A) occurs in the case the investigator is a qualified physician or dentist
b. Make reasonable efforts to ascertain the reasons for a subject's premature withdrawal from the trial
c. Encouraging subjects to report all Adverse Events (AEs)
d. Upon permission of the subject, inform primary physician of subject's participation in the trial
36
Why is it a good idea to develop standard procedures? (Select all that apply)
a. To assign responsibility
b. To promote compliance
c. To ensure that the trial is run consistently
d. To practice logical thinking skills
a. To assign responsibility
b. To promote compliance
c. To ensure that the trial is run consistently
37
A non-English speaking subject has responded to a recruitment ad to participate in a trial for treatment of her diabetes. She arrives at the site with her daughter who is fluent in English. The informed consent forms are only available in English. What actions are compliant with GCP?
a. Find a member of the clinic staff who speaks the same language as the subject to serve as the interpreter.
b. Contact the IRB/IC and ask for an exemption to screen subject.
c. Call the sponsor to request a translation of the informed consent.
d. Ask the subject's daughter to serve as interpreter and read the consent form to the subject.
c. Call the sponsor to request a translation of the informed consent.
38
The investigator at a big research center asked the monitor to complete the drug accountability forms as the site staff was not able to complete this on time before the Quality Control (QC) visit of the monitor. How should the monitor respond best?
a. The monitor should not respond and ask advice from their manager on how to act.
b. The monitor should refuse kindly and ask the site staff to complete the drug accountability forms.
c. The monitor should do as the investigator asks because the investigator is the leader of the trial.
d. The monitor should suggest to collaborate with the site staff and complete the drug accountability forms together at the occasion of the site visit.
b. The monitor should refuse kindly and ask the site staff to complete the drug accountability forms.
39
An investigator is willing to lead the conduct of a clinical trial if the sponsor allows deviations from the protocol to accommodate the trial subjects. How should the sponsor react to this request?
a. The sponsor should refuse this request as no protocol changes are ever allowed.
b. The sponsor should state that each request would need to be considered for a possible amendment prior to allowing any deviations.
c. The sponsor should ask the local regulatory bodies for advice.
d. The sponsor should allow this as the investigator is responsible for trial conduct.
b. The sponsor should state that each request would need to be considered for a possible amendment prior to allowing any deviations.
40
During a routine monitoring visit the monitor finds out the Informed Consent Form (ICF) of one of the subjects enrolled in the trial was NOT personally dated by the subject. What is the BEST corrective action to be taken by the monitor?
a. The monitor should leave as is and make a note of it in the monitoring visit report.
b. The monitor should ask the site staff to inform the IRB/IEC of the error.
c. The monitor should ask the site staff to discuss the issue with the subject and document the discussion in the source documents.
d. The monitor should ask the site staff to take action and have the subject date personally and provide an explanation of the change on the original IF.
d. The monitor should ask the site staff to take action and have the subject date personally and provide an explanation of the change on the original ICF.
41
A Clinical Research Coordinator (CRC) adjusted the dose of the Investigational Product (IP) for subject as the subject was suffering from Adverse Events (AEs) like headaches and vomiting. When is a CRC allowed to do this task?
a. Only when the CRC is a qualified physician
b. Only under the supervision of another site staff member who is named on the signature and delegation log
c. Never
d. Always; patient safety comes first
a. Only when the CRC is a qualified physician
42
A monitor is making corrections on the Case Report Form (CRF) during a monitoring visit and asks the site staff (as identified on the signature and delegation log) to sign and date these corrections.
This is an accepted way of working because:
a. Anybody can complete the CRF
b. The sponsor is ultimately responsible for the quality of the trial data and the investigator only needs to document the corrections.
c. It does not matter who makes the corrections on the CRF (sponsor representatives or ite staff identified on the signature and delegation log) as long as they are made when necessary, endorsed by the investigator, and documented.
d. The monitor is best suited to make those changes because he/she is considered the experts on the protocol.
c. It does not matter who makes the corrections on the CRF (sponsor representatives or ite staff identified on the signature and delegation log) as long as they are made when necessary, endorsed by the investigator, and documented.
43
In general, unused investigational drugs:
a. Can be kept for the next study
b. Can be destroyed by the investigator or pharmacy
c. Can be re-dispensed by the pharmacy
d. Must be returned to the sponsor
d. Must be returned to the sponsor
44
How long is the follow up period for subjects after Adverse Events (AEs)?
a. One vear
b. It is specified in the protocol
c. Two years
d. Six months
b. It is specified in the protocol
45
Which of the following statements would be unacceptable in a consent form?
a. In the event of any injury related to this research, you will be given medical treatment.
b. I waive any possibility of compensation for injuries that I may receive as a result of participation in this research.
c. Your participation in this research is voluntary. If you choose not to participate but change your mind later, your decision will not affect your relationship with your doctor.
b. I waive any possibility of compensation for injuries that I may receive as a result of participation in this research.
46
One of the primary purposes of a Phase I study is to:
a. Demonstrate long term safety and efficacy
b. Determine the metabolic and pharmacologic action of the drug in humans
c. Demonstrate efficacy within the established safe dose range
d. Gather information on additional indications for the drug
Determine the metabolic and pharmacologic action of the drug in humans
47
What is the purpose of the 'Data and Safety Monitoring Board (DSMB)'?
a. To approve the trial protocol
b. To ensure that the monitor is performing his/her duties correctly
c. To assess the progress of a clinical trial, the safety data, and the critical efficacy endpoints
d. To ensure the accuracy of data and to carry out data analysis
c. To assess the progress of a clinical trial, the safety data, and the critical efficacy endpoints
48
What does the IRB/IC evaluate? (select all that apply)
a. The subject-selection procedure
b. The rights, safety, and well-being of the subjects participating in the trial
c. The scientific tenability of the trial
d. The contract between the sponsor and investigator
a. The subject-selection procedure
b. The rights, safety, and well-being of the subjects participating in the trial
c. The scientific tenability of the trial
49
Which of the following documents is the investigator obliged to comply with during the trial? (select all that apply)
a. The sponsor's desire to present the investigational product in the best possible light
b. All applicable laws and regulations
c. ICH-GCP
d. The trial protocol
b. All applicable laws and regulations
c. ICH-GCP
d. The trial protocol
50
What is the purpose of the initiation visit? (Select all that apply)
a. To carry out source documentation verification
b. To review standard procedures
c. To review the blank Case Report Forms (CRFs)
d. To review the protocol
b. To review standard procedures
c. To review the blank Case Report Forms (CRFs)
d. To review the protocol
51
Who is ultimately responsible for Source Data Verification (SDV)?
a. The coordinator
b. The subject
c. The monitor
d. The investigator
c. The monitor
52
T/F Every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject.
True
53
The Declaration of Helsinki was developed by:
a. The Nuremberg tribunal
b. The World Medical Association
c. The government of Finland
d. The American Medical Association
b. The World Medical Association
54
This phase determines therapeutic benefit and is usually done in a larger, specific population.
a. Phase 1
b. Phase 2
c. Phase 3
d. Phase 4
c. Phase 3
55
This phase begins after drug approval and explores therapeutic use:
a. Phase 1
b. Phase 2
c. Phase 3
d. Phase 4
d. Phase 4
56
This is the most typical study. Investigates human pharmacology. It is the initial administration or an investigational new drug into humans. It is most commonly done in healthy subjects.
a. Phase 1
b. Phase 2
c. Phase 3
d. Phase 4
a. Phase 1
57
Providing a unified standard for Europe US, and Japan to facilitate the acceptance of clinical trials is the...
a. Mission statement of the ICH
b. Mission statement of the Declaration of Helsinki
a. Mission statement of the ICH
58
During the trial, who is responsible for communicating with the IRB/IC?
a. The pharmacist
b. The sponsor
c. The monitor
d. The investigator
d. The investigator
59
Which of the following individuals could be members of an IRB/IC? (Select all that apply)
a. The sponsor
b. Lay people
c. Trial Subjects
d. Medical professionals
b. Lay people
d. Medical professionals
60
In what format should approval be received from the IRB/IEC?
a. Electronic
b. Verbal
c. Personal
d. Written
d. Written
61
How can an Adverse Drug Reaction (ADR) be defined?
a. As an investigational drug that requires a second drug to be taken in order for the first one to be effective
b. As a noxious and unintended response to the investigational drug
c. As a positive response to the investigational drug
d. As an investigational drug that prevents any other drug from being effective
b. As a noxious and unintended response to the investigational drug
62
Which of the following would be most appropriate for Adverse Event (A) reporting?
a. Telling subjects to only report Serious Adverse Events (SAEs)
b. Documenting and reporting all Adverse Events (As). However trivial they may appear to be
c. Only documenting Adverse Events (AEs) if more than one subject reports the event
d. Only informing subjects about the Serious Adverse Events (SAEs) that are likely to occur
b. Documenting and reporting all Adverse Events (As). However trivial they may appear to be
63
Which of the following criteria is described in ICH-GCP as necessary for classifying an Adverse Event
(AE) as an Adverse Drug Reaction (ADR)?
a. That a causal relationship is at least a reasonable possibility
b. That a causal relationship is a definite possibility
c. That a causal relationship is a strong possibility
d. That a causal relationship is a very strong possibility
a. That a causal relationship is at least a reasonable possibility
64
Why is an estimand useful?
Estimands can be a useful way of
- clarifying the exact research question being evaluated in a study to specify target attributes
- avoid misinterpretation
- to ensure that study methods are aligned to the overall study objectives.
65
How are treatment effects measured in a clinical trial?
Estimating outcomes, collecting and analyzing data
66
What information needs to be included in the subject's medical records? (Select all that apply)
a. Medical history
b. Occurrence of AE's
c. Randomization number
d. Name of the monitor
a. Medical history
b. Occurrence of AE's
c. Randomization number
67
Which groups of potential subjects are mentioned in ICH-GCP as being 'vulnerable subjects'? (Select all that apply)
a. Junior members of the medical profession
b. People with heart conditions
c. Employees of the pharmaceutical industry
d. Members of the armed forces
a. Junior members of the medical profession
c. Employees of the pharmaceutical industry
d. Members of the armed forces
68
Who conducts clinical research Quality Control (QC) activities?
a. Investigator
b. Inspector
c. Monitor
d. Site staff
c. Monitor
69
T/F According to the Declaration of Helsinki, physicians may use an unproven intervention.
True
70
What is the minimum amount of time after formal discontinuation of the clinical development of an investigational product that essential documents should be retained according to ICH-GCP?
a. 16 years after the last marketing application approval in an ICH-GCP region
b. 4 years after the last marketing application approval in an ICH-GCP region
c. 2 years after the last marketing application approval in an ICH-GCP region
d. 8 years after the last marketing application approval in an ICH-GCP region
c. 2 years after the last marketing application approval in an ICH-GCP region
71
T/F Medical research with a vulnerable group is only justified if the research is responsive to the health needs or priorities of this group and it cannot be carried out in a non-vulnerable group. In addition, this group should stand to benefit from the knowledge, practices or interventions that result from the research.
True
72
What is the minimum time frame in which the investigator / institution must submit written trial progress reports to the IRB/IEC?
At least annually
73
To whom must adverse events and or laboratory abnormalities identified in the protocol as critical to safety evaluation be reported?
Investigator/institution, regulatory authorities
74
Who has authority to prematurely suspend or terminate a trial?
Sponsor, investigator, or IRB/IEC
75
Regardless of who terminates or suspends a trial, who must provide a detailed written explanation of the termination or suspension?
Sponsor
76
What details need to be documented in the subject source documentation when an AE occurs?
1. the severity of the event
2. when the event occurred
3. setting in which the event occurred
77
What is the difference between severe and serious?
Severe describes the intensity of a specific event. Serious describes an event in which the patient was at risk of death.
78
Who is responsible for designing the clinical trial protocol?
Sponsor
79
What are the 3 special populations mentioned in ICH E8?
1. pregnant women
2. nursing women
3. children
80
T/F: the intention of ICH E8 is to describe internationally accepted principles and practices in the conduct of both individual clinical trials and overall development strategy for new medicinal products
True
80
According to ICH E8, what are response variables that are chosen to assess the drug's effects?
study endpoints
81
Per ICH E8, methods used to evaluate patient usage of the test drug should be what?
Specified in the protocol and actual usage documented
82
T/F: The DSMB is a separate entity from an IRB/IEC?
True
83
What is the purpose of the DSMB?
to assess the progress of a clinical trial, the safety data, and the critical efficacy endpoints
84
Which variable in a study should be used to determine the sample size?
primary variable
85
When writing an early phase clinical study plan, what do you pay attention to, if you wish to maximize the chance of observing specific clinical effects of interest?
Target Population
86
Which ICH guidance pertains to the pediatric population?
ICH E11
87
What type of trial is the study of how the organism effects the drug for the duration of exposure?
Pharmacokinetic Trial
88
What type of trial examines the drug's effect on the organism for the duration of exposure?
Pharmacodynamic Trial
89
What type of trial provides a specific treatment to study its impact on cancer?
Therapeutic Trial
90
What is the effect on data variability, if the CI is wide?
The wider the CI, the more data variability
91
Why do we need clinical trial statistical analyses?
To estimate treatment risks and benefits for a larger population
92
What is an Intercurrent Event?
An event occurring after treatment start that may complicate interpretation of treatment effects during statistical analysis.. note, intercurrent events should not be actively avoided.
93
What FDA document must all investigators sign prior to participating in a drug clinical trial?
FDA form 1572 - a legally binding document designed to inform clinical investigators of their research obligations and secure the investigator's commitment to follow pertinent FDA regulations
94
What is the purpose of a 1572 form?
1) to provide the sponsor with information about the investigator's qualifications and the clinical site that will enable the sponsor to establish and document that the investigator is qualified and the site is an appropriate location at which to conduct the clinical investigation, and
2) to inform the investigator of his/her obligations and obtain the investigator's commitment to follow pertinent FDA regulations.
95
Generally, the sponsor will enter into a clinical trial_____(CTA) with the investigator. This is a contract that defines both the terms of study conduct and the financial agreements.
Agreement
96
By signing the Form _____ _____ the investigator enters into a legally binding contract with the FDA.
FDA 1572
97
The investigator is also required to provide evidence that he or she is qualified to properly conduct the trial through submission of an up to date...
CV
98
What do sensitivity analyses test?
Data robustness
99
A sponsor is developing an IP for treatment of a medical condition where there is one additional marketed product approved for treatment of the condition. The sponsor believes their product works as well or better than the current treatment with fewer side effects. What is the most-likely study design they will use to test the efficacy of the IP?
Non-Inferiority
100
What type of clinical trial most likely requires enrollment of the largest number of research subjects?
Therapeutic confirmatory
101
Minimum number of members on an IRB/EC
5 .. lay people and medical professionals can be part of the IRB/EC
102
Who are vulnerable subjects?
- Junior members of the medical profession
- Employees of a pharmaceutical company
- Military personnel
- Pregnant Women
- Prisoners
103
ICH E6 section 3.4 and 21 CFR 56.115 both state that the IRB/IC should retain all relevant records for ----- years after completion of the trial
3
104
What is the status of ICH in US?
It is a FDA guidance
105
A second study drug is given on Day 7 to counteract the toxicity of Drug 1. Subject #4-706 is given Drug 1 on Day 1. Due to a snowstorm, Subject 4-706 is delayed for several days before returning to the site for Drug 2. Missing the administration of Drug 2 on Day 7 placed the subject at risk of significant toxicity.
This event required the subject be notified of the increased risk and required close monitoring of the subject by phone.
Is this a UP? Is this an AE?
This is an unanticipated problem that does not include an adverse event
106
A subject received the wrong study drug resulting in severe nausea and vomiting, and a visit to the emergency room for treatment. The subject notified the study coordinator the day after the emergency room visit. The study coordinator reviewed the subject's study records and discovered the error. The coordinator notified the subject of the study drug error, which caused the nausea and vomiting. The investigator notified the IRB and the IRB approved a revision of the standard pharmacy procedure for administering investigational drugs.
Is this a UP? Is this an AE?
This is an unanticipated problem, which resulted in an adverse event
107
Housekeeping employees of the medical center were recruited for a federally funded study of blood pressure, blood count levels, infectious disease history, and job stress. The interviews and blood tests were conducted in a private location not affiliated with the study center. Follow-up interviews were conducted in the same location. The study coordinator stopped at the cafeteria on her way back to the study office after the second study visit for the last three study subjects and lost the three file folders.
Records of one subject indicated he had a history of a STD and another had recently been treated for TB.
The subjects were notified of the loss. Following this event, the IRB approved a protocol change requiring that all records be transmitted electronically to the study office using the medical center's secure network.
Is this a UP? Is this an AE?
This is an unanticipated problem and not an adverse event
108
An investigational biologic administered to the first two subjects in a Phase II clinical trial was not appropriately screened for two viral contaminants, HIV and Hep B, due to human error in the screening process. Follow-up testing indicated that the subjects and their partners were not infected. The subjects and others were notified of the increased risk.
Is this a UP?
This is an unanticipated problem requiring notification to the IRB and FDA
109
What are the criteria of an UP?
1) unexpected
2) related
3) greater risk of harm
110
ICH guidelines cover what 4 main categories?
Quality, Safety, Efficacy, Multidisplicinary
111
Adults with more than a 12 month history of migraines were assigned randomly in a double-blinded study to receive treatment with experimental drug X (10 or 20 mg/day) or placebo. The primary effect measure was the reduction in severity of the migraine attacks. Enrollment was 1200 subiects. Which of the following best describes the clinical phase of this study?
Phase III
112
Long-term toxicology of an experimental drug in animals most likely refers to which part of drug development?
Preclinical
113
Pharmacokinetics and pharmacodynamics of a new formulation of an investigational drug most likely refers to which clinical phase of a study in humans?
Phase I
114
For a Phase I new drug study in humans, what is the primary source of the data included in the initial IB?
Preclinical data
115
The goal of the ----- is to standardize technical guidelines and requirements for drug marketing registrations, so that applications for marketing to various regulatory agencies around the world can occur without redundant testing.
ICH
116
Compliance with ---- standards enhances protection of study subjects and the integrity of the data collected during a trial.
GCP
117
What are the 10 elements of informed consent?
1. Purposes of research
2. Expected duration of participation
3. Description of procedures and identification of experimental procedures
4. Description of foreseeable risks or discomforts
5. Description of any benefits to subject or others
6. Disclosure of alternative procedures or course of tx
7. Description of confidentiality records
8. Explanation of compensation or medical tx available if injury occurs
9. Contact for answers to pertinent questions about research and subjects rights and who to contact in the event of research related injury
10. Statement that participation is voluntary and participation can be discontinued without penalty
118
What rights does direct access give a member of a regulatory authority, sponsor, monitor, or auditor?
permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial
119
A sponsor proposes research to evaluate reengineering a commercially available pacemaker. It is hoped that the new pacemaker will pose fewer risks to individuals when compared to the current commercially available products. How should this device be classified?
Significant risk device
120
What are the three principles discussed in the Belmont Report?
Respect for persons, beneficence, justice
121
The Belmont Report's principle of respect for persons incorporates at least 2 ethical convictions. What are they?
first, that individuals should be treated as autonomous agents, and that persons with diminished autonomy are entitled to protection
122
Three elements of the consent process are...
information, comprehension, voluntariness
123
According to the US Federal Research Misconduct Policy, falsification involves:
Manipulating research materials, equipment, or processes, or changing or omitting data
124
A CRA is preparing to conduct a pre-study visit. Which of the following documents should be the BEST resource for answers to the investigator's questions regarding the rationale for investigating the investigational product, the dose and regimen, and the risk/benefit ratio?
a. Investigator's Brochure
b. Phase 1 Study Reports
c. Sample Informed Consent Form
d. Investigators' Meeting Handouts
Investigator's Brochure
125
Who is responsible for the investigational product at a site during the study?
a. The Investigator
b. The Sponsor
c. The Monitor
d. The Pharmacist
a. The Investigator
126
An Investigator is reviewing a protocol for a Phase 1 study. Which one of the following is most likely to be its objective? To determine the...
... safety and efficacy of agent "X" versus placebo in alleviating pain in patients with osteoarthritis.
... therapeutic dosage of an investigational product in reducing soft tissue inflammation following third molar extractions.
... dosage at which caffeine enhances acetylsalicylic acid absorption in normal, healthy volunteers.
... PSA levels over time in patients with benign prostatic hypertrophy treated with a herbal extract.
... dosage at which caffeine enhances acetylsalicylic acid absorption in normal, healthy volunteers.
127
Potentially vulnerable subjects who require special consideration by an IRB/IEC include which of the following? 1. Medical, pharmacy, dental, and nursing students 2. Prisoners 3. Elderly patients living at home 4. Serving military personnel
2, 3 and 4 only
1, 2 and 3 only
1, 2 and 4 only
1, 3 and 4 only
1, 2 and 4 only
128
All of the following are likely stratification factors in a randomization schedule EXCEPT:
Glucose Level
Caloric Intake
Disease Severity
Prior Study Participation
Prior Study Participation
129
A protocol for a new drug for the treatment of cystic fibrosis (CF) excludes patients who have received either antibiotics or corticosteroids within 2 weeks of screening, as well as patients who have started a new chronic medication for CF within 2 weeks of screening. Using these criteria, which of the following patients would be INELIGIBLE to participate in this study?
- A patient who was diagnosed 2 weeks ago with allergic rhinitis for which a nasal antihistamine was prescribed to be taken on a p.r.n. basis.
- A patient who was admitted to the hospital one month ago and was put on IV antibiotics for a pulmonary infection and discharged after 3 days with a 1-week course of oral antibiotics.
- A patient who is on longstanding treatment with prednisone to maintain pulmonary functions.
- A patient who was seen in the emergency department 10 days ago for symptoms presenting as a migraine headache. The patient was treated with an injection of pethidine and discharged.
A patient who is on longstanding treatment with prednisone to maintain pulmonary functions.
130
Which of the following must be described in a protocol?
- Information on the bio-availability of the investigational product.
- Names and addresses of the responsible independent ethic committee(s).
- The statistical methods to be employed.
- The quality assurance auditing procedures.
The statistical methods to be employed.
131
When reviewing a protocol, the schedule of study events would most likely be presented in? 1. The Protocol 2. The Investigator's Brochure 3. An Appendix to the Protocol 4. The Informed Consent Form
1 and 2 only
1 and 3 only
2 and 4 only
3 and 4 only
1 and 3 only
132
A crossover design is BEST described as a study...
... with a placebo run-in.
... where only responders receive long term therapy.
... where subjects receive all study treatments at different times.
... where each dose of investigational product has a matching placebo.
... where subjects receive all study treatments at different times.
133
A study subject develops drug-induced nephritis and is admitted to the hospital. Which answer describes this situation best?
a. An adverse drug reaction.
b. An unexpected adverse drug reaction.
c. A serious adverse drug reaction.
d. A life-threatening adverse drug reaction.
A serious adverse drug reaction
133
During a clinical trial, which of the following are considered Serious Adverse Events? 1. Prolonged hospital stay because of an infection following surgery 2. Hospital admission following a motor vehicle accident 3. Severe rash 4. Pregnancy resulting in the normal delivery of twins
1 and 2 only
1 and 3 only
2 and 4 only
3 and 4 only
1 and 2 only
133
According to ICH GCP, the best description of an AE or ADR that is serious is one which is...
Fatal or life-threatening, results in or prolongs inpatient hospitalization, results in persistent disability/incapacity, a congenital anomaly/birth defect.
All of the above plus cancer and overdose.
Fatal and life-threatening only.
An overdose of the study drug.
Fatal or life-threatening, results in or prolongs inpatient hospitalization, results in persistent disability/incapacity, a congenital anomaly/birth defect.
134
Which of the following are considered tasks that the CRC would complete prior to a routine monitoring visit by a CRA? 1. Review the CRFs to ensure all data to date has been transcribed. 2. Enter all projected visit dates on the enrollment log. 3. Record investigational product dispensation completed to date. 4. Send the original CRF pages to the CRA for review.
1 and 2 only
1 and 3 only
2 and 3 only
3 and 4 only
1 and 3 only
135
When training the investigator on a phase 3 trial, which of the following protocol sections is MOST important to emphasize?
The statistical plan.
The pre-clinical data.
The publication policy.
The efficacy variables.
The efficacy variables
136
At the close-out visit, the CRA notices that a subject has omitted information on a baseline diary. Which of the following is the BEST advice for the CRA to give the investigator?
Ask the subject to complete the diary now.
Fill in the information based on subsequent data.
Discard the incomplete diary.
Document this information as missing.
Document this information as missing
136
What action should be taken by the investigator or subinvestigator for any discrepancies between source documents and CRF?
Highlight with a fluorescent pen.
Refer to the IRB/IEC.
Provide an explanation.
No action required.
Provide an explanation
137
ICH GCP requires an investigator to provide the IRB/IEC with all of the following EXCEPT:
Details of expenses that will be paid to subjects.
Significant protocol changes.
Names of all subjects whose participation in the study is terminated prematurely.
A written explanation if a study is terminated or suspended by the sponsor.
Names of all subjects whose participation in the study is terminated prematurely.
138
Investigators must send the IRB/IEC the following reports:
Annual progress report
Monitoring visit report
Study initiation report
Patient enrollment tracking report
Annual progress report
139
A document on which the subject records their consumption of study medication at home is called a:
Case report form
Subject enrollment log
Subject diary
Investigational product accountability log
Subject diary
140
A CRA is responsible for which of the following during a monitoring visit? 1. Verifying subject protection 2. Confirming data recorded are verifiable from source documents 3. Reviewing medical charts for potential subjects 4. Ensuring protocol compliance
1, 2 and 3 only
1, 2 and 4 only
1, 3 and 4 only
2, 3 and 4 only
1, 2 and 4 only
141
An investigator is about to start a trial with seriously ill patients. He encounters a subject in a life-threatening situation for which no standard acceptable treatment is available. The investigator believes that the investigational drug may benefit this patient, who is unconscious and time is not sufficient to obtain informed consent from a legally acceptable representative. The investigator determines that the investigational drug is the only means available to increase the possibility of preserving the patient's life and decides to administer the investigational product. According to ICH GCP, which of the following is true in relation to the IRB/IEC and their approval (favorable opinion) about this emergency use:
Under no circumstances can unconscious patients be enrolled without either their consent or that of their legally acceptable representative.
A physician who is independent of the trial must confirm the need to treat the unconscious patient with the investigational product.
The investigator is responsible for medical care of trial subjects so can enroll unconscious patients without prior IRB/IEC approval.
Documented approval or favorable opinion from the IRB/IEC is needed for a protocol involving unconscious patients before they can be enrolled.
Documented approval or favorable opinion from the IRB/IEC is needed for a protocol involving unconscious patients before they can be enrolled.
142
The PRIMARY responsibility of an IRB/IEC is to:
Evaluate the liability of the investigator.
Ensure all participating subjects are protected.
Ensure all participating subjects sign an informed consent form.
Verify the risk/benefit ratio of the investigational product
Ensure all participating subjects are protected.
143
Which of the following are Essential Documents held in a site's Trial Master File? 1. List of staff to whom the Investigator has delegated significant trial related duties. 2. Investigational product accountability records. 3. Subject screening logs. 4. Signed informed consent forms.
1, 2 and 3 only
1, 2 and 4 only
1, 3 and 4 only
2, 3 and 4 only
2, 3 and 4 only
144
An IRB/IEC is required to retain records for at least how many years after completion of a trial?
2 years
3 years
5 years
10 years
3 years
144
When the investigator or his/her team make changes or corrections to a CRF, which action should they take?
Over-write the original entry.
Write them in red ink in the margin.
Ensure that they are all explained.
Initial and date each correction.
Initial and date each correction.
145
An experienced PI was not available to attend the investigator's meeting for a multi-center study. The PI now discovers a conflict prohibiting attendance at the site initiation meeting, but all other study team members are confirmed to attend in 2 days time. Which of the following is the best course of action?
Reschedule the initiation meeting.
Confirm that the investigator's experience with the investigational product is current.
Hold the initiation meeting as scheduled and review content with the investigator at the earliest opportunity.
Request that study staff review the initiation meeting content with the investigator and produce meeting minutes.
Reschedule the initiation meeting.
146
A subject is reviewing an informed consent for a hypertension study with the CRC. The consent includes a lengthy paragraph on discomforts and risks. The subject remarks about this and is concerned. Which of the following is the MOST appropriate response?
The regulatory authorities require that all known and possible side effects be listed.
Hypertension medications can cause numerous side effects, but most are not serious.
The investigator will be available to answer your questions before the screening examination starts.
This is a reference list for collecting relevant data on adverse events occurring during the study.
The investigator will be available to answer your questions before the screening examination starts.
147
Which is the most important document when preparing for an audit?
Investigator's Brochure
Monitoring Guidelines
Trial Master File
Trial Protocol
Trial Master File
148
What is a non-clinical study?
A study performed outside a clinic (e.g., at a general practitioner or in a Phase 1 Center).
A study not performed on human subjects.
A study performed in healthy volunteers.
A study using an external medical device in patients with heart disease.
A study not performed on human subjects.
149
Quality control of clinical trials by sponsors includes: 1. The use of SOPs 2. Pre-trial visits to assess suitability of sites 3. Monitoring visits 4. Inspections
1, 2 and 3
1, 2 and 4
1, 3 and 4
2, 3 and 4
1, 2 and 3
150
Who has ultimate responsibility for the quality and integrity of the data in a contracted trial?
The Contract Research Organization
The Sponsor
The Regulatory/Competent Authority
An Independent Data Monitoring Committee
The Sponsor
151
When metabolites are studied, what must be studied?
Pharmacokinetic profiles
152
If a potential for drug-drug interaction is suggested by a metabolic profile, what is recommended
Including studies focused on drug-drug interactions
153
When working with special populations such as renal/hepatic dysfunction patient populations, what should be considered?
Pharmacokinetic studies to assess the impact of potentially altered drug metabolism or excretion directly related to disease
154
When should pregnant subjects be included in clinical trials?
When drug being studied is intended to be used in pregnant women but generally pregnant women
155
What should happen if a patient becomes pregnant during trial participation with an IP?
IP treatment should be discontinued if it can be done safely and follow-up on pregnancy and with fetus and then child is very important
156
When nursing mothers are enrolled in clinical trials, who else should be monitored as part of the mother's participation?
The babies should be monitored for effects of the drug as the drug or its metabolites may be excreted into the mothers' milk
157
What aspects of clinical trials should be defined in a written protocol before the study starts?
1) Objectives
2) Design
3) Conduct
4) Analysis
5) Reporting
158
At the month-3 visit of a Phase III double-blind trial, the subject informs the CRC that he was seen in the emergency department for an anaphylactic reaction. The subject states, “The doctor told me I was very lucky. I might have died.” Having received this information, the MOST appropriate sequence of action is to inform:
a. PI
b. Sponsor
c. IRB/IEC
d. All of the above
All of the above
159
A subject is upset and wants to know whom she should contact regarding her rights as a research subject. The CRC should tell her to contact the
A. PI
B. regulatory authority
C. risk management department
D. individual listed in the ICF
D. individual listed in the ICF
160
The trough blood level for a once-daily drug should be drawn how long after the last dose?
A. immediately
B. 4 hours
C. 12 hours
D. 24 hours
D. 24 hours
Definition of trough (lowest serum concentration level of a drug). The trough level should be measured just before the administration of the next dose.
161
A CRC has received three subject complaints of localized infection at the venipuncture site. The CRC queries the phlebotomist and discovers that when the first stick is unsuccessful, any additional sticks are done with the same needle. This is in violation of the site’s SOPs. Which of the following actions should the CRC take? (Select all that apply)
1. Suggest review of proper specimen collection for the phlebotomist.
2. Document and report the findings.
3. Inform the IRB/IEC of the situation and the corrective action.
4. Report the incidents to the IDMC/DSMB.
1 and 2 only
162
All of the following are regulatory documents EXCEPT
A. informed consent
B. protocol signature page
C. laboratory certification
D. confidentiality agreement
D. confidentiality agreement
163
According to ICH Guidelines, the source document should contain which of the following information regarding informed consent?
A. time the consent form was signed by the subject
B. date the PI and subject signed the consent form
C. date and tiem the consent form was signed by the witness
D. evidence that the consent form was signed prior to trial-related procedures
D. evidence that the consent form was signed prior to trial-related procedures
164
A clinical trial is being conducted for hormone replacement. The trial includes a diary. Which of the following would be considered an objective parameter?
A. mood swings
B. breast tenderness
C. severity of hot flashes
D. episodes of vaginal bleeding
D. episodes of vaginal bleeding
165
A subject presents at a site with her husband, after pre-qualifying on a phone screen. She states that she is legally blind and cannot read the ICF. A Braille ICF is not available. This subject is able to sign her name if her hand is guided to the signature line. Which of the following is the BEST course of action to obtain legal consent for this subject?
A. The subject and an impartial witness can sign the ICF after it is read to them and she verbally states her understanding.
B. Her husband can sign the ICF for her after it has been read to the subject and she verbally states her understanding.
C. The subject does not qualify as she is unable to read the ICF herself and a Braille consent form is not available.
D. An investigator must co-sign the ICF after it has been read to the subject and she verbally states her understanding and has signed the ICF.
A. The subject and an impartial witness can sign the ICF after it is read to them and she verbally states her understanding.
166
A small biotech company is investigating the anti-tumoral potential of scorpion toxin in high grade recurrent brain tumors. After animal trials have been completed, the first trial in humans would MOST likely involve (Select all that apply)
1. healthy volunteers.
2. pharmacokinetic analysis.
3. placebo control.
4. dose escalation.
2 and 4 only
167
A competent adult subject signs a consent form with an “X” and indicates approval. Which of the following is the BEST action for the CRC to take?
A. Have the consent form notarized.
B. Exclude the subject from the trial.
C. Document why the subject signed with an “X”
D. Have the legal guardian sign the informed consent form.
C. Document why the subject signed with an “X”
168
In addition to obtaining a signed informed consent form, which of the following should be documented in the research record? (Select all that apply)
1. the time and date that the procedures will be performed
2. that the subject’s questions were answered
3. the names of people present during the consent process
4. that no trial procedures were performed prior to consenting
C. 2 and 4 only
169
A sponsor has supplied all sites with digital thermometers for a vaccine trial. At one site, the CRC notices that 10 of 30 subjects have recorded consistently low temperature readings in their diaries for the first 7 days of the trial. Upon review with the subjects, there were no related complaints. Which of the following should be the CRC’s FIRST action?
A. Notify the sponsor.
B. Contact the manufacturer
C. Inform the remaining 20 subjects.
D. Replace existing thermometers with an alternate model.
A. Notify the sponsor.
170
A potential subject for a trial has been mailed an ICF prior to his screening visit. When the subject arrives at the research department for his screening visit, he states he read the ICF and is ready to do the trial. He does not have the copy of the ICF that was mailed to his home with him. According to the ICH Guidelines, which of the following are the BEST actions for the CRC to take initially? (Select all that apply)
1. Have the subject sign the ICF.
2. Document that the subject reviewed the ICF at home.
3. Tell the subject to keep the ICF mailed to the home as his copy.
4. Confirm the subject’s understanding of the ICF.
1 and 4 only
171
A sponsor/investigator (investigator-initiated research) expands a trial from a single site to four trial sites in different areas of the country. The sponsor/investigator should do which of the following? (Select all that apply)
1. Monitor compliance with GCP.
2. Report AEs to the sites.
3. Keep investigators informed of new findings.
4. Update investigators regarding subject recruitment.
1 and 3 only
172
At a trial site, CRCs perform quality assurance as needed throughout the progress of their trials. A CRC notes that five of the seven research nurses failed to document subject understanding of the trial. Which of the following actions should the CRC perform? (Select all that apply)
1. Inform the sponsor of this practice.
2. Revise the delegation of responsibility.
3. Ensure the subjects have been well informed of the trial.
4. Review the informed consent process with the individual research nurses.
3 and 4 only
173
A subject is issued 120 tablets and is instructed to take 2 tablets 4 times a day. He returns 88 tablets on the morning of day 9 fasting for laboratory tests. What percent compliant is he?
50%
