Other Reading Flashcards
What do usual measures of adverse effects include?
1) reasons participants are taken off study medication or device removed
2) reasons participants are on reduced dosage of study medication or on lower intensity of intervention
3) type and frequency of participant complaints
4) laboratory measurements, including x-rays
5) in long-term studies, possible intervention-related reasons participants are hospitalized
6) combinations or variations of any of the above
Fundamentals of Clincial Trials, 3rd edition
Friedman/Furberg/DeMets
What is the Common Rule?
1991 agreement to cover all federally-sponsored and federally-conducted research by a common set of regulations
Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick
What is beneficense?
doing no harm, maximizing benefits while minimizing risks
Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick
What is/are Kefauver-Harris Amendments?
Amendment to FD&C act that requires informed consent for experimental drugs
Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick
What are CIOMS guidelines?
International Ethics Guidelines for Biomedical Research Involving Human Subjects
Developed by the Council for International Organizations of Medical Sciences in 1982 to guide cross-cultural research
Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick
What is the PPRA?
Protection of Pupil Rights Amendment
Department of Education regulation that states that surveys, questionnaires and instructional materials for school children must be inspected by parents/guardians
Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick
Title 21 CFR _____________
Title 45 CFR _____________
(fill in the blanks)
21: Food and Drugs
45: Public Welfare
Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick
The Nuremberg Code stated that:
- informed consent of volunteers must be obtained without coercion in any form
- human experiments should be based upon prior animal experimentation
- anticipated scientific results should justify the experiment
- only qualified scientists should conduct medical research
- physical and mental suffering and injury should be avoided
- there should be no expectation of death or disabling injury from the experiment
true
false
true
Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick
The Declaration of Helsinki varied from the Nuremberg Code in what ways? (mark all that apply)
a) consent for non-therapeutic research
b) allowed for enrolling certain patients in therapeutic research without consent
c) allowed legal guardians to grant permission to enroll subjects in research
d) none of the above
b) allowed for enrolling certain patients in therapeutic research without consent
c) allowed legal guardians to grant permission to enroll subjects in research
Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick
The role of deception in human subject research continues to be debated even today. The Nuremberg Code, the Declaration of Helsinki, and the Belmont Report point to the importance of obtaining consent that is informed, understood and voluntary. The federal regulations specifically allow for deception in research.
true
false
true
…but only in limited conditions and only with institutional review board approval.
Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick
In 1974, Congress passed the _______________. The Act required regulations for the protection of human subjects that included requirements for informed consent and review of research by institutional review boards (IRBs).
(fill in the blank)
National Research Act
Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick
The Belmont Report
The principle of beneficence is applied in ___________.
(fill in the blank)
risk/benefit assessments
The Belmont Report
The principle of justice is applied in the _____________.
(fill in the blank)
selection of research subjects
The Belmont Report
The principle of respect for persons is applied in the _____________.
fill in the blank
consent process
Vulnerable subjects include:
(mark all that apply)
a) children
b) some mentally incapacitated
c) individuals with dementia and other cognitive disorders
d) prisoners
e) pregnant women
f) elderly
g) terminally ill and hospitalized patients
h) students
i) employees
all
What is FERPA?
Family Educational Rights and Privacy Act
Except under certain circumstances involving treatment, subpoena, educational or financial aid, FERPA requires that written permission must be obtained to disclose personally identifiable information from a student’s educational records.
What is PPRA?
Protection of Pupil Rights Amendment
Survey research in schools is regulated under PPRA. This law states that surveys, questionnaires and instructional materials can be inspected by parents or guardians; and parental permission must be obtained to allow minors to participate in a survey revealing information such as mental and psychological problems, sexual behavior and attitudes, illegal behavior, etc.
Informed consent is a process of information exchange that takes place between the prospective subject and the investigator when?
a) before the study
b) during the study
c) after the study
a, b, and c
With regard to information provided during the informed consent process, for judging how much and what sort of information should be provided, a standard of “the reasonable subject” should be used.
true
false
true
This implies that the extent and nature of information provided should be such that a reasonable person has enough information to decide whether or not to participate in the research.
______ occurs when an overt threat of harm is intentionally presented by one person to another in order to obtain compliance.
______, by contrast, occurs through an offer of an excessive, unwarranted, inapproproate or improper reward or other overture to obtain compliance.
(fill in the blank)
coercion
undue influence
Justice is relevant to the selection of subjects of research at which two levels?
social and individual
What are the three main protective mechanisms established in the Common Rule?
1) review of research by an IRB
2) informed consent of subjects
3) institutional assurances of compliance
Protecting Study Volunteers in Research
p 37
What is an FWA?
Federal-Wide Assurance
Before a federal grant or contract can be awarded, the institution must file an “Assurance of Compliance” with the government. In the Assurance, the institution agrees to apply the federal regulations, and to be guided by the ethical principles of the Belmont Report.
A Federal_Wide Assurance is only required for federally sponsored research; however, must institutions voluntarily choose to extend the procedures and protections to all research conducted at the institution.
c 2004
What are the two main purposes of GCP?
1) to protect human subjects during clinical studies
2) to protect patients who might receive approved products in the future
There is no one source of guidance for GCPs.
true
false
true
They are embodied within laws, regulations and guidelines such as:
- ethical codes
- IRB and consent regulations
- guidelines on the obligations of investigators, sponsors and monitors
- Code of Federal Regulations pertaining to drugs and devices
- ICH Guidelines
- official guidance documents
Payments to research subjects is considered a benefit.
true
false
false
It is a recruitment incentive.
Exemption from IND/IDE regulations is an exemption from IRB review.
true
false
false
Protecting Study Volunteers in Research
p 63
The back of the 1572 lists the commitments the investigator is making to the FDA for conduct of the study. These commitments come right from the regulations that govern investigations drugs (i.e., part 312).
true
false
true
The Form FDA 1572 is often referred to as the “hanging paper” because it is a criminal offense to sign the document if it contains false information or if commitments made within the signed document are ignored.
An FDA-approved IDE application is required prior to human subject exposure for all device studies.
true
false
false
…for all significant-risk device studies
There is no Form FDA 1572 for device studies.
true
false
true
However, documentation of similar commitments by the investigators is required in either the IDE application or in the sponsor’s contracts with investigators.
Study Process for Industry-Sponsored Studies
The investigator responsibilities critical to the conduct of industry-sponsored studies include which three additional processes?
1) investigational materials handling and accountability
2) adverse events
3) documentation
What are DARs?
drug or device accountability records
Adverse Events - Device Requirements
The regulations require that investigators prepare and submit complete, accurate and timely reports of unanticipated adverse device effects to the sponsor and to the reviewing IRB as soon as possible, but no later than ___ business days after the investigator learns of the effect.
a) 5
b) 10
c) 15
d) 30
b) 10
Investigators are advised to contact the study sponsor before any study related records are destroyed to ensure compliance with the regulatory requirements.
true
false
true
IND or IDE application
The investigator-sponsor is required to wait 30 days for FDA review prior to enrolling subjects in a study. If no notice is received within that 30-day period that indicates that the FDA has no concerns with the application, the IND or IDE is considered to be approved.
true
false
true
It is advisable, however, to call the FDA to confirm that they do not have any issues or concerns with the application.
Investigator-sponsors are required to notify the FDA and all participating investigators in writing of any adverse experience that is serious, related and unexpected.
The report must be filed with the FDA no more than ___ calendar days after the investigator-sponsor initially receives the information.
a) 5
b) 10
c) 15
d) 30
c) 15
The reporting requirements for adverse device effects are different from those for drugs and biologics. The investigator must conduct an evaluation of any unanticipated adverse device effect.
If found that the effect presents an unreasonable risk to subjects, investigations must be terminated as soon as possible but no later than ___ working days after sponsor makes determination.
This also must occur within ___ working days of when the investigator-sponsor was notified for the adverse effect.
(fill in the blanks)
5
15
so basically, evaluation must be conducted within 10 days max
notification to termination is 15 days max
What is a Certificate of Confidentiality?
Certificates of Confidentiality are issued to the NIH to protect the privacy of research subjects by protecting investigators and institutions from being compelled to release information that could be used to identify subjects in a research study.
They allow the investigator to refuse to disclose identifying information on research participants in any civil, criminal, administrative, legislative or other proceeding, whether at the federal, state, or local level.
All clinical gene transfer trials are subject to FDA regulations (21 CFR 312) as biological products.
true
false
true
Gene transfer is a technique to substitute absent or faulty genes causing diseases with working genes, so that cells make the correct enzyme or protein.
Regarding gene transfer trials…
The roles of the IBC (Institutional Biosafety Committee) and IRB overlap when considering human subjects protection.
true
false
true
While many IBCs have minimal experience with clinical settings, many IRBs have little knowledge of the technical issues associated with the gene transfer.
All clinical trials require safety monitoring, but not all trials require a DMC.
true
false
true
The FDA draft guidance specifically states that Data Monitoring Committees (DMCs) should be established for controlled trials where mortality and major morbidity serve as the primary or secondary endpoints.
c 2004
???gone beyond draft guidance now???
The scope of research affected by the HIPAA Privacy Rule is _____________ the Common Rule’s (45 CFR 46, Subpart A) or the FDA regulations (21 CFR Parts 50 and 56).
a) different from
b) the same as
c) similar to
a) different from
The HIPAA Privacy Rule affects any research use or disclosure of PHI.
Liability for HIPAA Noncompliance include (mark all that apply):
a) civil monetary penalties up to $100 per violation
b) criminal penalties include up to $250,000 in fines
c) civil monetary penalties up to $25,000 per person/entity per year for each HIPAA standard that is violated
d) criminal penalties include a maximum of 10 years imprisonment
e) civil penalties only
f) criminal penalties only
a, b, c, and d
The Privacy Rule does not apply to de-identified data.
true
false
true
In a __________ study, neither the participants nor the investigators responsible for following the participants know the identity of the intervention assignment.
double-blind
The main advantage of a truly double-blind study is that the risk of bias is reduced.
An outside body needs to monitor data for toxicity and benefit, especially in long-term trials.
Fundamentals of Clinical Trials
Friedman
pg 85
A ________ is a participant who, although assigned to the control group, follows the intervention regimen; or a participant who, assigned to an intervention group, follows either the control regimen or the regimen of another intervention group when more than one intervention is being evaluated.
The _______ design uses each participant twice, once as a member of the control group and once as a member of the intervention group.
crossover
crossover
drop-in: unidirectional - person assigned to control group but begins following the intervention
drop-out: person assigned to intervention group who fails to comply with intervention regimen
If control group is either on placebo or non no standard intervention, the drop-out is equivalent to a crossover.
Fundamentals of Clinical Trials
Friedman
pg 205, 42
___________ control studies are comparative studies with an intervention group and a control group; the assignment of the participant to a group is determined by the formal procedure of _________.
Randomized
randomization
Fundamentals of Clinical Trials
Friedman
pg 43
______ are people who are screened as potential participants for a randomized trial but who do not meet all of the entry criteria and, therefore, are not randomized.
Exclusions
reasons: age, severity of disease
Exclusions influence interpretation of results of clinical trial. An investigator may determine whether most high-risk people were excluded or whether the initial assumption was incorrect.
Fundamentals of Clinical Trials
Friedman
pg 285
A properly planned and executed clinical trial is a powerful experimental technique for assessing the effectiveness of an intervention.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 2
The study population should be defined in advance, stating unambiguous inclusion (eligibility) criteria. The impact that these criteria will have on study design, ability to generalize, and participant recruitment must be considered.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 30
Each clinical trial must have a primary question. The primary question, as well as any secondary or subsidiary questions, should be carefully selected, clearly defined, and stated in advance.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 16
Sound scientific clinical investigation almost always demands that a control group be used against which the new intervention can be compared. Randomization is the preferred way of assigning participants to control and intervention groups.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 42
Randomization tends to produce study groups comparable with respect to known and unknown risk factors, removes investigator bias in the allocation of participants, and guarantees that statistical tests will have valid significance levels.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 61
A clinical trial should, ideally, have a cross-over design to avoid potential problems of bias during data collection and assessment. In studies where such a design is impossible, a single-blind approach and other measures to reduce potential bias are favored.
true
false
false
…ideally, have a double-blind design…
Fundamentals of Clinical Trials
Friedman
pg 82
Clinical trials should have sufficient statistical power to detect differences between groups considered to be of clinical interest. Therefore calculation of sample size with provision for adequate levels of significance and power is an essential part of planning.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 94
Relevant baseline data should be measured in all study participants before the start of intervention.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 130
Successful recruitment depends on developing a careful plan with multiple strategies, maintaining flexibility, establishing interim goals, and preparing to devote the necessary effort.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 141
During the initial phase of a study, sufficient effort should be spent to ensure that all key data critical to the interpretation of the trial are of high quality.
true
false
false
…during all phases of a study…
Fundamentals of Clinical Trials
Friedman
pg 157
Adequate attention needs to be given to the assessment, analysis, and reporting of adverse effects to permit valid assessment of potential risks of interventions.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 170
Assessment of the effects of interventions on participants’ health-related quality of life (HRQL) may be an important component of clinical trials, especially those that involve interventions directed at primary or secondary prevention of chronic disease.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 186
Many potential adherence problems can not be prevented or minimized before participant enrollment. Once a participant is enrolled, taking measures to enhance and monitor participant adherence is essential.
true
false
false
…adherence problems can be prevented…
Fundamentals of Clinical Trials
Friedman
pg 205
Survival analysis methods are important in trials where participants are entered over a period of time and have various lengths of follow-up. These methods permit the comparison of the entire survival experience during the follow-up and may be used for the analysis of time to any dichotomous response variable such as a nonfatal event or an adverse effect.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 223
During the trial, response variables need to be monitored for early dramatic benefits or potential harmful effects. Preferably, monitoring should be done by a person or group independent of the investigators. Although many techniques are available to assist in monitoring, none of them should be used as the sole basis for the decision to stop or continue the trial.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 246
Excluding randomized participants or observed outcomes from analysis and subgrouping on the basis of outcome or response variables can reduce biased results of unknown magnitude or direction.
true
false
false
…response variables can lead to biased results…
Fundamentals of Clinical Trials
Friedman
pg 284
The closeout of a clinical trial is usually a fairly complex process that requires careful planning if it is to be accomplished in an orderly fashion.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 323
The sponsors have an obligation to review their study and its findings critically and to present sufficient information so that readers can properly evaluate the trial.
true
false
false
The investigators have an obligation…
Fundamentals of Clinical Trials
Friedman
pg 334
Anyone responsible for organizing and conducting a multicenter study should have a full understanding of the complexity of the undertaking. Problems in conduct of the trial most often originate from inadequate and unclear communication between the participating investigators, all of whom must agree to follow a common study protocol.
true
false
true
Fundamentals of Clinical Trials
Friedman
pg 345
The purpose of an IRB is to:
a) inform study subjects about the protocol and drug
b) protect the rights and welfare of human subjects of research
c) ensure that sponsors are meeting FDA regulations
d) write easily understood consent forms
e) ensure that only innovative new drugs are studies
b) protect the rights and welfare of human subjects of research
The CRCs Guide to Coordinating Clinical Research
The investigator must obtain IRB approval of the study and the consent form:
a) before the study has been completed
b) before enrolling any patients in the study
c) before receiving any grant money for the study
d) within one month of starting the study
e) before the first patient has completed the study
b) before enrolling any patients in the study
The CRCs Guide to Coordinating Clinical Research
What is form FDA 2522?
Transmittal of Annual Reports for Drugs and Biologics for Human Use
Guide to Clinical Trials
p 1011
Annual reports are submitted within 60 days of the anniversary date of approval of the application using form FDA 2252.
An ___________________ is a research permit to allow an unapproved medical device to be tested on humans to evaluate safety and efficacy.
Investigational Device Exemption (IDE)
Guide to Clinical Trials
p 1011
A ________________ is a permit to allow the sale of a Class III medical device. This application is usually filed after completion of clinical trials that assure safety and effectiveness of the device or that establish an acceptable performance standard.
Premarket Approval Application (PMA)
Guide to Clinical Trials
p 1011
What is form FDA 356h?
Application to Market a New or Abbreviated New Drug or Biologic for Human Use
Guide to Clinical Trials
p 1010
An _____________ is a type of clinical trial in which both the researchers and participants know which treatment is being administered. This contrasts with single blind and double blind experimental designs, where participants are not aware of what treatment they are receiving (researchers are also unaware in a double blind trial).
open-label trial or open trial
Open-label trials may be appropriate for comparing two very similar treatments to determine which is most effective. An open-label trial may be unavoidable under some circumstances, such as comparing the effectiveness of a medication to intensive physical therapy sessions.
An open-label trial may still be randomized. Open-label trials may also be uncontrolled, with all participants receiving the same treatment.
http://en.wikipedia.org/wiki/Open-label_trial
________________ is a notice to the FDA, Center for Devices and Radiological Health, of the intent to market a medical device of Classes I (those subject to only the general controls of the Food, Drug, and Cosmetic Act) or II (those that are or will be subject to a performance standard in accordance with the FD&C Act).
Premarket Notification (510k)
Guide to Clinical Trials
p 1010
The IRB must inform the investigator the study has been approved by:
a) written notification saying it has been approved
b) a visit or phone call from the IRB chairperson
c) a preliminary call followed by written minutes of the meeting
d) the IRB informs the sponsor, who in turn informs the investigator by shipping drug
e) the IRB informs the institution administration, who then informs the investigator
a) written notification saying it has been approved
The CRCs Guide to Coordinating Clinical Research
For initial approval of proposed research, the investigator must submit to the IRB:
a) a protocol synopsis and the investigator brochure
b) the informed consent and a protocol synopsis
c) the full protocol
d) the full protocol and the informed consent
e) the investigator brochure
d) the full protocol and the informed consent
The CRCs Guide to Coordinating Clinical Research
Any proposed advertising for the study:
a) must be submitted to the IRB and approved before it can be used
b) can be used as long as the IRB has approved a similar ad in the past
c) must be submitted to the IRB for information, but it is not approved
d) must come from the sponsor, since the sponsor pays for it
d) must be submitted before the study can start
a) must be submitted to the RIB and approved before it can be used
The CRCs Guide to Coordinating Clinical Research
Any amendment that __________ must be approved by the IRB prior to implementation.
a) increases the risk to subjects
b) decreases the number of subjects
c) changes the protocol in any way
d) all of the above
e) none of the above
a) increases the risk to subjects
The CRCs Guide to Coordinating Clinical Research
Which of the following are necessary to waive consent?
a) subject is unable to give consent
b) no time or unable to contact next of kin
c) life-threatening condition
d) no other treatment available
e) none of the above
f) all of the above
f) all of the above
The CRCs Guide to Coordinating Clinical Research
The investigator’s signature must be on the consent form.
true
false
false
The CRCs Guide to Coordinating Clinical Research
There may be instances where a DMC may detect a greater frequency of serious adverse events in one arm of a controlled study. This finding, reported to the sponsor as part of a recommendation to modify the study, would be considered serious and unexpected, and the sponsor would be required to report this to the FDA as well as to all other study investigators.
true
false
true
Protecting Study Volunteers in Research
p 138
Exemptions to the IND process apply as long as the product is used according to the product labeling (dose, duration, patient population, etc.).
true
false
true
Protecting Study Volunteers in Research
p 63
Prior to the initial shipment of test articles, there must be documentation indicating that the necessary IDE or IND is filed and active, and that the site’s IRB has reviewed and approved the study.
true
false
true
Protecting Study Volunteers in Research
p 67
_______ documentation is where the information is first recorded, including medical records and case report forms.
Source
Protecting Study Volunteers in Research
p 70
The investigator-sponsor is to notify the FDA by telephone of any unexpected, fatal or life-threatening experience associated with the use of a drug in clinical studies conducted under the IND.
true
false
true
Protecting Study Volunteers in Research
p 73
For this purpose only, the FDA defines life-threatening as the subject being at immediate risk of death from the reaction
The investigator-sponsor is to notify the FDA by telephone of any unexpected, fatal or life-threatening experience associated with the use of a drug in clinical studies conducted under the IND within _______ calendar days after receiving the information.
a) 5
b) 7
c) 10
d) 15
b) 7
Protecting Study Volunteers in Research
p 73
Sponsors of INDs for marketed drugs are required to report adverse events associated with the use of the drug that occur outside of the studies conducted under their INDs.
true
false
false
…are NOT required…
Protecting Study Volunteers in Research
p 73
However, if such information affects the perceived risks to the subjects in the clinical trials, the information needs to be shared with the investigators and their respective IRBs.
The reporting requirements for adverse device effects are ___________ those for drugs and biologics.
a) the same as
b) similar to
c) different from
c) different from
Protecting Study Volunteers in Research
p 74
The investigator-sponsor must immediately conduct an evaluation of any unanticipated adverse device effect.
If this effect present an unreasonable risk to subjects, the investigator-sponsor is required to terminate all investigations as soon as possible, but no later than 5 working days after the sponsor makes this determination.
This also must occur within 15 working days of when the investigator-sponsor was notified for the adverse effect.
The _________ is responsible for recommending trial termination when subject safety is jeopardized.
a) investigator
b) sponsor
c) DMC
d) monitor
c) DMC (data monitoring committee)
Protecting Study Volunteers in Research
p 137
Know the following abbreviations.
a) ACHRE
b) CRC
c) CFR
d) DMC
e) DSMB
f) DHHS
g) FERPA
h) FDA
i) GCP
j) IBC
k) IRB
l) ICH
m) IDE
n) IND
o) NBAC
p) NIH
q) NDA
r) OCR
s) OHRP
t) ORI
u) PI
v) PHI
w) PPRA
x) PHS
y) RAC
a) Advisory Committee on Human Radiation Experiments
b) clinical research coordinator
c) Code of Federal Regulations
d) data monitoring committee
e) data safety monitoring board
f) Department of Health and Human Services
g) Family Educational Rights and Privacy Act
h) Food and Drug Administration
i) good clinical practice
j) institutional biosafety committee
k) institutional review board
l) International Conference on Harmonization
m) Investigational Device Exemption
n) Investigational New Drug Application
o) National Bioethics Advisory Commission
p) National Institutes of Health
q) new drug application
r) Office of Civil Rights
s) Office for Human Research Protection
t) Office of Research Integrity
u) principal investigator
v) protected health information
w) Protection of Pupil Rights Amendment
x) Public Heath Service
y) Recombinant DNA Advisory Committee
Protecting Study Volunteers in Research
p 362-365
An investigator’s brochure is required of sponsors, and recommended but not required of sponsor- investigators.
true
false
true
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM446695.pdf
In some circumstances, even if a sponsor-investigator
is required to submit an IND, the IND may not
need to include all of the information required for an IND submission.
true
false
true
For example, if a sponsor-investigator is proposing to evaluate a drug that is the subject of an existing IND, a sponsor-investigator can seek a letter of cross-reference authorization from the sponsor of that IND (called the
commercial sponsor) that permits the sponsor-investigator to refer the FDA to the information contained in the commercial sponsor’s IND. If the sponsor-investigator is studying an FDA-approved prescription or nonprescription drug, even if an IND is required, some of the information needed for an IND submission can be found in the FDA-approved labeling.
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM446695.pdf
The sponsor-investigator’s signature on Form FDA 1572 is a commitment to obtain IRB approval before initiating the trial.
true
false
true
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM446695.pdf
If the FDA makes the determination within the 30-day review period that the trial should be placed
on clinical hold, the FDA will notify the sponsor-investigator as soon as possible after making that determination (usually by telephone) to not initiate the trial.
true
false
true
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM446695.pdf
Charging for the investigational drug is only permitted in rare circumstances, and then only with prior written approval by the FDA.
true
false
true
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM446695.pdf
Responsible parties have a statutory obligation to update clinical trial registration information on
ClinicalTrials.gov (42 U.S.C. 282(j)(4)(C)).
true
false
true
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM446695.pdf
What is FDA Form 3674?
a) Application to Market a New or Abbreviated New Drug or Biologic for Human Use
b) Certificate of Compliance
c) Transmittal of Annual Reports for Drugs and Biologics for Human Use
b) Certificate of Compliance
Form 3674 must accompany an application/submission, including certain amendments, supplements, and
resubmissions, submitted under §§ 505, 515, 520(m), or 510(k) of the Federal Food, Drug, and Cosmetic Act
or § 351 of the Public Health Service Act.
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM354618.pdf
What is FDA Form 356h?
a) Application to Market a New or Abbreviated New Drug or Biologic for Human Use
b) Certificate of Compliance
c) Transmittal of Annual Reports for Drugs and Biologics for Human Use
a) Application to Market a New or Abbreviated New Drug or Biologic for Human Use
What is FDA Form 2252?
a) Application to Market a New or Abbreviated New Drug or Biologic for Human Use
b) Certificate of Compliance
c) Transmittal of Annual Reports for Drugs and Biologics for Human Use
c) Transmittal of Annual Reports for Drugs and Biologics for Human Use
The Privacy Rule actually covers a broader scope of research activities than does the Common Rule.
true
false
true
Some research that is exempt from the Common Rule’s requirements is not exempt from the Privacy Rule
Protecting Study Volunteers in Research
p 170
The process by which a subject voluntarily confirms his or her willingness to participate in a clinical trial is known as:
a) HIPAA authorization
b) IRB approval
c) legally authorized agreement
d) intent to treat
e) informed consent
e) informed consent
The CRCs Guide to Coordinating Clinical Research
Informed consent is documented by:
a) a written, signed and dated informed consent form
b) a witness signature
c) the IRB chairperson
d) the investigator
e) the subject’s legally authorized representative
a) a written, signed and dated informed consent form
The CRCs Guide to Coordinating Clinical Research
Which signatures are required by regulation to be on the consent form?
a) the investigator
b) the subject
c) the investigator and the subject
d) the subject and a witness
e) the investigator, the subject and a witness
b) the subject
The CRCs Guide to Coordinating Clinical Research
ICH guidelines provide a unified standard for __________ clinical trials involving human subjects.
a) designing
b) conducting
c) recording
d) reporting
e) all of the above
e) all of the above
The CRCs Guide to Coordinating Clinical Research
What are the two main themes covered by the formal ICH definition of “Good Clinical Practice?”
a) rights and well-being of study subjects and compliance with regulations
b) rights and well-being of study subjects and credibility of the data
c) compliance with regulations and credibility of the data
d) compliance with the regulations and the formal marketing approval process
e) credibility of the data and international consistency
b) rights and well-being of study subjects and credibility of the data
The CRCs Guide to Coordinating Clinical Research
GCPs are derived from all of the following except:
a) safety surveillance systems
b) Federal regulations
c) ethical codes
d) ICH guidelines
e) official guidance documents
a) safety surveillance systems
The CRCs Guide to Coordinating Clinical Research
Non-clinical studies refer to studies that do not involve:
a) animal testing
b) drugs
c) human subjects
d) toxicolgy parameters
e) safety
c) human subjects
The CRCs Guide to Coordinating Clinical Research
In which development phase might normal, healthy volunteers be given a new drug?
a) Phase I
b) Phase II
c) Phase III
d) Phase IIIB
e) Phase IV
a) Phase I
The CRCs Guide to Coordinating Clinical Research
Large multicenter studies are usually done in:
a) Phase I
b) Phase II
c) Phase III
d) Phase IIIB
e) Phase IV
c) Phase III
The CRCs Guide to Coordinating Clinical Research
One of the primary purposes of a Phase II study is to:
a) demonstrate long-term safety and efficacy
b) gather information on additional indications for the drug
c) demonstrate efficacy within the established safe dose range
d) familiarize physicians with the drug
c) demonstrate efficacy within the established safe dose range
The CRCs Guide to Coordinating Clinical Research
By regulation, an investigator must keep records relating to:
a) disposition of the study drug
b) case histories
c) case report forms
d) signed informed consent forms
e) all of the above
e) all of the above
The CRCs Guide to Coordinating Clinical Research
Most sponsors will expect an investigative site to keep all study records for:
a) 15 years
b) 3 years
c) 5 years
d) until the sponsor says they may be destroyed
e) 2 years after the last subject finished treatment
d) until the sponsor says they may be destroyed
The CRCs Guide to Coordinating Clinical Research
Which of the following should be kept separately from other study documents?
a) signed consent forms
b) grant information
c) IND safety reports
d) IRB communications
e) screening logs
b) grant information
The CRCs Guide to Coordinating Clinical Research
A source document is any document where:
a) lab values are shown
b) HIPAA authorization was received
c) data are first recorded
d) a subject’s name is shown
e) sponsor access to the document is not allowed
c) data are first recorded
The CRCs Guide to Coordinating Clinical Research
Standard operating procedures (SOPs) are essential for:
a) standardizing processes
b) ensuring that regulatory requirements are met
c) training new personnel
d) managing workload
e) all the above
e) all the above
The CRCs Guide to Coordinating Clinical Research
SOPs are:
a) written descriptions of how tasks are to be performed
b) legally binding on employees
c) usually provided by the sponsor
d) required by regulations
e) all of the above
a) written descriptions of how tasks are to be performed
The CRCs Guide to Coordinating Clinical Research
Once an SOP is in place, it should never be changed.
true
false
false
The CRCs Guide to Coordinating Clinical Research
In general, a sponsor will not place a study at a site without:
a) an on-site IRB
b) a study coordinator
c) an assurance that the study will enroll at least a given number of subjects
d) an assurance that there will be no staff turnover during the study
e) at least one sub-investigator who is a physician
b) a study coordinator
The CRCs Guide to Coordinating Clinical Research
A competing study can be one that is ongoing in:
a) the site
b) the same clinic or hospital
c) the community
d) only a and b
e) a, b, and c
e) a, b, and c
The CRCs Guide to Coordinating Clinical Research
Some of the questions an investigator and a CRC should ask when assessing protocol feasibility at their site include all the following except:
a) will the sponsor pay at least 30% of the grant in advance?
b) have we worked with this sponsor before and was the partnership successful?
c) is the number of subjects to be enrolled realistic?
d) is the study scientifically sound?
e) is the IRB apt to have problems with any aspects of this protocol?
a) will the sponsor pay at least 30% of the grant in advance?
The CRCs Guide to Coordinating Clinical Research
Most sponsors operate on which kind of basis when it comes to grant payments?
a) 20% up front
b) the entire grant paid in one up-front payment
c) fee-for-service
d) payment for each subject when the subject completes the trial
e) payment upon request from the investigator
c) fee-for-service
The CRCs Guide to Coordinating Clinical Research
Financial disclosure applies to:
a) only the investigator
b) the investigator and the CRC
c) anyone at the site who is involved in the trial
d) only those people listed on the 1572
e) the investigator, the CRC, and the pharmacist
d) only those people listed on the 1572
The CRCs Guide to Coordinating Clinical Research
Investigator meetings are a requirement for any multicenter study with six or more sites.
true
false
false
The CRCs Guide to Coordinating Clinical Research
Study initiation meetings are usually held:
a) at least 2 months before the study starts
b) after the site has received all study materials and is ready to start enrollment
c) after the first two subjects have been enrolled
d) before the investigator meeting
e) at the sponsor’s place of business
b) after the site has received all study materials and is ready to start enrollment
The CRCs Guide to Coordinating Clinical Research
One of the most difficult aspects of doing clinical trials is:
a) following the protocol
b) finding a good coordinator
c) recruiting sufficient subjects
d) working with the pharmacy
e) obtaining a high enough grant
c) recruiting sufficient subjects
The CRCs Guide to Coordinating Clinical Research
The FDA considers advertising for study subjects to be:
a) part of the consent process
b) necessary for all trials
c) acceptable only in phase I trials
d) never appropriate with vulnerable populations of subjects
e) acceptable only in print media, as opposed to radio and television ads
a) part of the consent process
The CRCs Guide to Coordinating Clinical Research
Payments to subjects in clinical trials should:
a) never be done
b) be done only for phase I trials
c) be done only with prior IRB approval
d) be done only once, at the end of the subject’s trial involvement
e) never be more than $100 for completing a study
c) be done only with prior IRB approval
The CRCs Guide to Coordinating Clinical Research
Potential reasons to discontinue a subject in a trial are:
a) the subject is not compliant with study procedures
b) the subject has intolerable medical events during treatment
c) pregnancy
d) a and b
e) a, b, and c
e) a, b, and c
The CRCs Guide to Coordinating Clinical Research
Visit windows are:
a) always plus and minus 2 days
b) determined by the investigator
c) the number of days around a specific date that the patient may come in for a study visit
d) the number of visits included in a protocol
e) a percentage of the total days in a protocol divided by the number of visits
c) the number of days around a specific date that the patient may come in for a study visit
The CRCs Guide to Coordinating Clinical Research
Patient compliance with study drug dosing is a statistical issue, so site personnel do not have to be concerned about it.
true
false
false
The CRCs Guide to Coordinating Clinical Research
Which of the following should not be included in a protocol?
a) a description of the objectives and purpose of the study
b) the inclusion and exclusion criteria for study subject
c) the design of the study
d) the amount of the grant per subject
e) the investigator’s responsibilities
d) the amount of the grant per subject
The CRCs Guide to Coordinating Clinical Research
Case report forms are usually completed by:
a) the investigator
b) the CRC
c) the CRA
d) the subject
e) the sponsor
b) the CRC
The CRCs Guide to Coordinating Clinical Research
In general, corrections to case report forms should be made by:
a) the CRA
b) the data entry person
c) the CRC or the investigator
d) only the investigator
e) the person who finds the error
c) the CRC or the investigator
The CRCs Guide to Coordinating Clinical Research
It is a regulatory requirement to have a source document for every data item collected on case report forms.
true
false
false
The CRCs Guide to Coordinating Clinical Research
The most common reason for a study to be closed at a site is:
a) the study is complete
b) the drug was found to be ineffective
c) there were safety problems with the drug
d) lack of enrollment
e) falsification of data
a) the study is complete
The CRCs Guide to Coordinating Clinical Research
By regulation, investigators are required to make a final study report to:
a) the FDA and the sponsor
b) the sponsor and the IRB
c) the institution
d) the sponsor, IRB, and FDA
e) the sponsor
b) the sponsor and the IRB
The CRCs Guide to Coordinating Clinical Research
There are two main reasons that a sponsor might audit a study site. They are:
a) the IRB has requested a sponsor audit
b) to ensure that the site is complying with the regulations and protocol
c) there is evidence that the site is out of compliance and the sponsor wants to verify whether or not this is true
d) a and b
e) b and c
e) b and c
The CRCs Guide to Coordinating Clinical Research
The FDA _____________ sponsor audit reports of a study site.
a) does not have routine access to
b) does have routine access to
c) will always receive a copy of
d) should receive from the investigator a copy of
e) will never see
a) does not have routine access to
The CRCs Guide to Coordinating Clinical Research
Which of the following is not one of the purposes of an FDA study-related or investigator-related audit?
a) to determine the validity of the data
b) to determine the integrity of the data
c) to determine that the drug was properly manufactured
d) to assess adherence to regulations and guidelines
e) to determine that the rights and safety of subjects were properly protected
c) to determine that the drug was properly manufactured
The CRCs Guide to Coordinating Clinical Research
In study-related audits by the FDA, the studies audited are usually:
a) just starting to enroll
b) about half done, but still enrolling new subjects
c) ongoing, but closed to new enrollment
d) closed
e) Phase IIIB studies
d) closed
The CRCs Guide to Coordinating Clinical Research
The two main aspects of a study that will be looked at by the FDA during an audit are:
a) study conduct and study data
b) study conduct and recruitment methods
c) study data and statistical methodology
d) drug storage conditions and pharmacy records
e) a and d above
a) study conduct and study data
The CRCs Guide to Coordinating Clinical Research
There are three classifications that result from an FDA audit. The one that means that deviations from the regulations were found but that they were not serious, is:
a) VAI.
b) NAI.
c) OAI.
d) BIMO-2.
e) EIR.
a) VAI.
The CRCs Guide to Coordinating Clinical Research
____ devices are subject only to general controls. They typically present the lowest potential for harm and are simpler in design than other classes of devices. Examples of these devices include elastic bandages, examination gloves, and hand-held surgical instruments.
a) Class I
b) Class II
c) Class III
a) Class I
http: //www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf
_____ devices are those for which general controls
alone are insufficient to provide a reasonable assurance of safety and effectiveness. In addition to complying with general controls, These devices are also subject to special controls identified by the agency, which may include special labeling requirements, performance standards and postmarket surveillance. Examples of these devices include powered wheelchairs, infusion pumps, and surgical drapes.
a) Class I
b) Class II
c) Class III
b) Class II
http: //www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf
_____ devices generally are those for which insufficient information exists to determine that general or special controls are sufficient to provide a reasonable assurance of safety and effectiveness. Examples of these devices include replacement heart valves, silicone gel-filled breast implants, and implanted cerebellar stimulators.
a) Class I
b) Class II
c) Class III
c) Class III
http: //www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf
An humanitarian use device (HUD) is a device that is intended to benefit patients in the treatment and diagnosis of diseases or conditions that affect or is manifested in fewer than ______ individuals in the United States per year.
a) 400
b) 1,400
c) 4,000
c) 4,000
http: //www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf
Humanitarian Use Devices
a) 21 CFR Part 314
b) 21 CFR Part 505
c) 21 CFR Part 600
d) 21 CFR Part 814
d) 21 CFR Part 814
http: //www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=814&showFR=1&subpartNode=21:8.0.1.1.11.7
A Humanitarian Device Exemption (HDE) application is similar to a PMA, but because a HUD is exempt from
the effectiveness requirements of a PMA, an HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating that the device is effective for its intended purpose. However, the HDE must contain sufficient information for FDA to determine that the probable benefit to health outweighs the risk of injury or illness, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment. Section 520(m)(2)(C).
true
false
true
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf
HUDs should not be used until AFTER the HDE applicant obtains approval of the HDE from FDA and the IRB approves its use. IRBs should ensure that HDE approval has been granted before approving the device for use at their institution.
true
false
true
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf
The IRB must review and approve individual uses of an HUD. The IRB may approve use of the HUD without any further restrictions.
trur
false
false
The IRB does not need to review and approve individual uses of an HUD, but rather the IRB may approve use of the device as it sees fit. That is, the IRB may approve use of the HUD without any further restrictions, under a protocol, or on a case-by-case basis.
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf
In some higher risk cases, IRBs have approved HUDs for a specific number of patients and have required a summary report before approving the use in additional patients.
true
false
true
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf
The act and the HDE regulations require informed consent when treating/diagnosing a patient with an HUD.
true
false
false
The act and the HDE regulations do not require informed consent. Because an HDE provides for
marketing approval, use of the HUD does not constitute research or an investigation which would normally require consent from the study subjects. However,
there is nothing in the law or regulations that prohibits a state or institution from requiring prospective informed consent, when feasible.
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf
Unless it is an emergency, before an HUD is used off-label, the agency recommends that the HDE holder obtain FDA approval of the use following the compassionate use policy for unapproved devices.
true
false
true
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf
Among other things, the FDA BIMO Program involves site visits to:
(mark all that apply)
a) IRBs
b) clinical investigators
c) sponsors
d) monitors
e) contract research organizations
f) nonclinical (animal) laboratories
g) bioequivalence analytical laboratories
a, b, c, d, e, f, g
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126555.pdf
FDA inspections of IRBs generally fall into one of two categories:
Surveillance inspections – periodic, scheduled inspections to review the overall operations and procedures of the IRB.
Directed inspections – unscheduled inspections focused on the IRB’s review of a specific clinical trial or trials. Directed inspections generally result from a complaint, clinical investigator misconduct, or
safety issues pertaining to a trial or site.
true
false
true
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126555.pdf
FDA’s inspection of clinical investigators is limited to the United States
true
false
false
International inspections are generally conducted when the studies are part of a marketing application submitted to FDA and provide data critical to decision-making on product approval.
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126555.pdf
In accordance with the CFR, which of the following is not an essential element of an informed consent document:
a) the statement, “a description of this clinical trial will be available on http://www.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.”
b) a disclosure statement of the financial information for the investigator and all study staff personnel involved in the conduct of the investigation
c) a statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject’s participation, a description of the procedures to be followed, and identification of any procedures which are experimental
d) a statement that participation is voluntary, that refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and that the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.
b) a disclosure statement of the financial information for the investigator and all study staff personnel involved in the conduct of the investigation
http: //socra.wcea.education/searchOnlineTraining#/training/133162
In accordance with the CFR, if the reviewing IRB/iEC disagrees with a non-significant risk (NSR) determination made by a sponsor, then the RIB/IEC shall notify:
a) the FDA
b) the sponsor
c) the potential subjects
d) the investigator and, where appropriate, the sponsor
d) the investigator and, where appropriate, the sponsor
http: //socra.wcea.education/searchOnlineTraining#/training/133162
The FDA defines a covered study [covered clinical trial] as “…any study of a drug, biological product or device in humans submitted in a marketing application or reclassification petition that the applicant or FDA relies on to establish that the product is effective (including studies that show equivalence to an effective product) or any study in which a single investigator makes a significant contribution to the demonstration of safety.”
true
false
true
http://en.wikipedia.org/wiki/Covered_clinical_study
A medical device pivotal study is a definitive study
in which evidence is gathered to support the safety and effectiveness evaluation of the medical device for its intended use.
true
false
true
Medical devices can undergo three general stages of clinical development. To begin, medical devices may
undergo an exploratory clinical stage. In this stage, the limitations and advantages of the medical device are evaluated. This stage includes first-in-human studies
and feasibility studies. The next stage, the pivotal
stage, is used to develop the information necessary
to evaluate the safety and effectiveness of the device for the identified intended use. It usually consists of one or more pivotal studies. Finally, devices undergo a post-
market stage which can include an additional study
or studies for better understanding of device safety,
such as rare adverse events and long-term effectiveness.
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM373766.pdf
What is an early feasibility study?
a) a limited clinical investigation of a device early in development, typically before the device design has been finalized, for a specific indication (e.g., innovative device for a new or established intended use, marketed device for a novel clinical application). It may be used to evaluate the device design concept with respect to initial clinical safety and device functionality in a small number of subjects (generally fewer than 10 initial subjects) when this information cannot practically be provided through additional nonclinical assessments or appropriate nonclinical tests are unavailable. Information obtained from this type of study may guide device modifications. It does not necessarily involve the first clinical use of a device.
b) a type of study in which a device for a specific indication is evaluated for the first time in human subjects.
c) a clinical investigation that is commonly used to capture preliminary safety and effectiveness information on a near-final or final device design to adequately plan an appropriate pivotal study. Because the study of a near-final or final device design takes place later in development than an early feasibility study, FDA would expect to see more nonclinical (or prior clinical) data in a traditional feasibility study IDE application. This type does not necessarily need to be preceded by an early feasibility study.
d) a clinical investigation designed to collect definitive evidence of the safety and effectiveness of a device for a specified intended use, typically in a statistically justified number of subjects. It may or may not be preceded by an early and/or a traditional feasibility study.
a) a limited clinical investigation of a device early in development, typically before the device design has been finalized, for a specific indication (e.g., innovative device for a new or established intended use, marketed device for a novel clinical application). It may be used to evaluate the device design concept with respect to initial clinical safety and device functionality in a small number of subjects (generally fewer than 10 initial subjects) when this information cannot practically be provided through additional nonclinical assessments or appropriate nonclinical tests are unavailable. Information obtained from an early feasibility study may guide device modifications. It does not necessarily involve the first clinical use of a device.
An early feasibility study is appropriate when device changes are expected and when, due to the novelty of the device or its intended use, a clinical study is expected to provide information that cannot be practically
obtained through additional nonclinical assessments.
An early feasibility study may be appropriate even if a device or a prototype of the device has previously been used clinically for the intended clinical use. Note
that not all novel devices or uses warrant an early feasibility study, nor would FDA mandate that an early feasibility study be conducted.
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM279103.pdf2
What is a first-in-human (FIH) study?
a) a limited clinical investigation of a device early in development, typically before the device design has been finalized, for a specific indication (e.g., innovative device for a new or established intended use, marketed device for a novel clinical application). It may be used to evaluate the device design concept with respect to initial clinical safety and device functionality in a small number of subjects (generally fewer than 10 initial subjects) when this information cannot practically be provided through additional nonclinical assessments or appropriate nonclinical tests are unavailable. Information obtained from this type of study may guide device modifications. It does not necessarily involve the first clinical use of a device.
b) a type of study in which a device for a specific indication is evaluated for the first time in human subjects.
c) a clinical investigation that is commonly used to capture preliminary safety and effectiveness information on a near-final or final device design to adequately plan an appropriate pivotal study. Because the study of a near-final or final device design takes place later in development than an early feasibility study, FDA would expect to see more nonclinical (or prior clinical) data in a traditional feasibility study IDE application. This type does not necessarily need to be preceded by an early feasibility study.
d) a clinical investigation designed to collect definitive evidence of the safety and effectiveness of a device for a specified intended use, typically in a statistically justified number of subjects. It may or may not be preceded by an early and/or a traditional feasibility study.
b) a type of study in which a device for a specific indication is evaluated for the first time in human subjects.
http: //www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM279103.pdf2
What is a traditional feasibility study?
a) a limited clinical investigation of a device early in development, typically before the device design has been finalized, for a specific indication (e.g., innovative device for a new or established intended use, marketed device for a novel clinical application). It may be used to evaluate the device design concept with respect to initial clinical safety and device functionality in a small number of subjects (generally fewer than 10 initial subjects) when this information cannot practically be provided through additional nonclinical assessments or appropriate nonclinical tests are unavailable. Information obtained from this type of study may guide device modifications. It does not necessarily involve the first clinical use of a device.
b) a type of study in which a device for a specific indication is evaluated for the first time in human subjects.
c) a clinical investigation that is commonly used to capture preliminary safety and effectiveness information on a near-final or final device design to adequately plan an appropriate pivotal study. Because the study of a near-final or final device design takes place later in development than an early feasibility study, FDA would expect to see more nonclinical (or prior clinical) data in a traditional feasibility study IDE application. This type does not necessarily need to be preceded by an early feasibility study.
d) a clinical investigation designed to collect definitive evidence of the safety and effectiveness of a device for a specified intended use, typically in a statistically justified number of subjects. It may or may not be preceded by an early and/or a traditional feasibility study.
c) a clinical investigation that is commonly used to capture preliminary safety and effectiveness information on a near-final or final device design to adequately plan an appropriate pivotal study. Because the study of a near-final or final device design takes place later in development than an early feasibility study, FDA would expect to see more nonclinical (or prior clinical) data in a traditional feasibility study IDE application. This type does not necessarily need to be preceded by an early feasibility study.
A traditional feasibility study or a pivotal study may be
more appropriate if the device design is near-final or final, respectively, depending on the amount of data available to justify the study.
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM279103.pdf2
What is a pivotal study?
a) a limited clinical investigation of a device early in development, typically before the device design has been finalized, for a specific indication (e.g., innovative device for a new or established intended use, marketed device for a novel clinical application). It may be used to evaluate the device design concept with respect to initial clinical safety and device functionality in a small number of subjects (generally fewer than 10 initial subjects) when this information cannot practically be provided through additional nonclinical assessments or appropriate nonclinical tests are unavailable. Information obtained from this type of study may guide device modifications. It does not necessarily involve the first clinical use of a device.
b) a type of study in which a device for a specific indication is evaluated for the first time in human subjects.
c) a clinical investigation that is commonly used to capture preliminary safety and effectiveness information on a near-final or final device design to adequately plan an appropriate pivotal study. Because the study of a near-final or final device design takes place later in development than an early feasibility study, FDA would expect to see more nonclinical (or prior clinical) data in a traditional feasibility study IDE application. This type does not necessarily need to be preceded by an early feasibility study.
d) a clinical investigation designed to collect definitive evidence of the safety and effectiveness of a device for a specified intended use, typically in a statistically justified number of subjects. It may or may not be preceded by an early and/or a traditional feasibility study.
d) a clinical investigation designed to collect definitive evidence of the safety and effectiveness of a device for a specified intended use, typically in a statistically justified number of subjects. It may or may not be preceded by an early and/or a traditional feasibility study.
http: //www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM279103.pdf2
The Federal government implemented the Health Insurance Portability and Accountability Act (HIIPAA) Privacy Rule in:
a) 1991
b) 1998
c) 2003
d) 2008
c) 2003
The CRC’s Guide to Coordinating Clinical Research
p 39
HIPAA regulations can be found in:
a) 21 CFR Parts 50 and 56
b) 21 CFR Part 54
c) 45 CFR Parts 160 and 164
d) 45 CFR Part 46
c) 45 CFR Parts 160 and 164
The CRC’s Guide to Coordinating Clinical Research
p 39
Emergency situations may arise in which there will be a need to use an investigational device in a manner inconsistent with the approved investigational plan or by a physician who is not part of the clinical study. _________________ of an unapproved device may occur before an IDE is approved.
a) emergency use
b) emergency research
c) compassionate use
d) treatment use
e) continued access
a) emergency use
http: //www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/ucm051345.htm#top
There are special cases under ______________ in which the human subject is in a life-threatening situation and it is not feasible to obtain informed consent. In order to allow such research to proceed, special provisions for exemption from informed consent requirements must be met.
a) emergency use
b) emergency research
c) compassionate use
d) treatment use
e) continued access
b) emergency research
http: //www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/ucm051345.htm#top
The ________________ provision allows access for patients who do not meet the requirements for inclusion in the clinical investigation but for whom the treating physician believes the device may provide a benefit in treating and/or diagnosing their disease or condition. This provision is typically approved for individual patients but may be approved to treat a small group.
a) emergency use
b) emergency research
c) compassionate use
d) treatment use
e) continued access
c) compassionate use
FDA recognizes that there are circumstances in which an investigational device is the only option available for a patient faced with a serious, albeit not life-threatening, disease or condition.
Prior FDA approval is needed before compassionate use occurs.
** aka Expanded Use **
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/ucm051345.htm#top
An approved IDE specifies the maximum number of clinical sites and the maximum number of human subjects that may be enrolled in the study. During the course of the clinical trial, if the data suggests that the device is effective, then the trial may be expanded to include additional patients with life-threatening or serious diseases. This is the ____________ provision.
a) emergency use
b) emergency research
c) compassionate use
d) treatment use
e) continued access
d) treatment use
The treatment use provision of the IDE facilitates the availability of promising new devices to desperately ill patients as early in the device development process as possible, before general marketing begins, and to obtain additional data on the device’s safety and effectiveness.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/ucm051345.htm#top
FDA may allow ____________ enrollment of subjects after the controlled clinical trial under an IDE has been completed in order to allow access to the investigational medical device while the marketing application is being prepared by the sponsor or reviewed by the FDA.
a) emergency use
b) emergency research
c) compassionate use
d) treatment use
e) continued access
e) continued access
Criteria: Public health need OR preliminary evidence that the device will be effective and there are no significant safety concerns.
Sponsors often propose a separate Continued Access study, independent from the pivotal trial but for the same patient population.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/ucm051345.htm#top
The medical product company must agree to provide the investigational drug for expanded access use. FDA cannot require a company to provide an investigational drug for expanded access use to proceed.
true
false
true
http://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/ucm20080392.htm#Expanded_Access_Requirements
A company may decide to turn down a request to provide [the investigational drug for expanded access use] if, for example it is not able or willing to provide access to an investigational drug outside of clinical trials intended to support marketing approval.
true
false
true
http://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/ucm20080392.htm#Expanded_Access_Requirements
A new early phase 1 trial is now sometimes substituted for this traditional testing (first-in-human trials). It is called a “microdosing” or phase 0 trial.
true
false
true
Conducting Clinical Research
p 12
________ studies are often large and multicentered and are considered primary efficacy studies, or pivotal trials in demonstrating a drug’s efficacy.
a) Phase 1
b) Phase 2
c) Phase 3
d) Phase 4
c) Phase 3
Conducting Clinical Research
p 13
______ studies are sometimes referred to as postmarketing studies or commitment studies.
a) Phase 1
b) Phase 2
c) Phase 3
d) Phase 4
d) Phase 4
Conducting Clinical Research
p 13
The FDA Amendments Act of 2007 established financial penalties for companies that failed to meet the timetables for their commitments (Phase 4 studies). The penalties start at $250,000 and “double every 30 days up to $1,000,000/30 day period or $10 million for all violations adjudicated in a single proceeding.”
true
false
true
Conducting Clinical Research
p 13
In a(n) ____________ , each participant is assigned to a specific treatment arm but all other study activities are the same for all participants.
a) parallel study
b) double-dummy protocol
c) open label study
d) single-blind study
e) double-blind study
a) parallel study
Conducting Clinical Research
p 20
In a(n) ___________, patients receive one medication for part of the trial and then a second one for the remainder. In other words, some subjects begin on drug A and then switch to drug B; others do the opposite.
a) parallel study
b) double-dummy protocol
c) open label study
d) crossover study
d) crossover study
Conducting Clinical Research
p 20
__________ means that in order to reduce bias, the study medications are disguised so that the subjects don’t know if they are receiving drug A or drug B
a) single-blind study
b) double-dummy protocol
c) open label study
d) crossover study
b) double-dummy protocol
Conducting Clinical Research
p 20
In a(n) _____________, all participants know which treatment the volunteers are receiving.
a) parallel study
b) double-dummy protocol
c) open label study
d) single-blind study
e) double-blind study
c) open label study
aka unblinded
Conducting Clinical Research
p 21
In a(n) ___________, the participants do not know the treatment assignment but the investigator and sponsor do.
a) parallel study
b) double-dummy protocol
c) open label study
d) single-blind study
e) double-blind study
d) single-blind study
Conducting Clinical Research
p 21
In a(n) __________, neither the investigator nor the subjects know the treatment assignments until well after the trial’s completion. A code is available for emergencies, however.
a) parallel study
b) double-dummy protocol
c) open label study
d) single-blind study
e) double-blind study
e) double-blind study
Conducting Clinical Research
p 21
Regarding devices, Sponsors make the initial decision as to what represents “significant risk,” although their decision can be challenged by the IRB or FDA.
true
false
true
Conducting Clinical Research
p 23
Similar to orphan drugs, a device can have a humanitarian device exemption (HDE) classification if the device will be used in fewer than 4,000 patients per year.
true
false
true
Conducting Clinical Research
p 24
Trials of devices that pose significant risk require clinical trials with IDE and FDA approval; those that pose a nonsignificant risk require IRB approval but not FDA approval.
true
false
true
Conducting Clinical Research
p 24
Device trials are much shorter than drug trials, with a total development time that may be less than 18 months. Similarly, the life cycle of the final product may well be less than 2 years, as new technologies lead to modifications and rapid obsolescence. This is very different than with drugs, many of which continue to be used for decades.
true
false
true
Conducting Clinical Research
p 25
Device trials may have more financial conflict-of-interest than drug trials because clinicians or inventors may have significant equity interests in the device and, because of their technical skills, be vital members of the initial device development team.
true
false
true
Conducting Clinical Research
p 27
The __________ markedly expands the scope of postmarketing surveillance studies and requires “active surveillance” for risks.
a) Clinical Trials Transformation Initiative
b) ClinicalTrials.gov
c) Genetic Information Nondiscrimination Act
d) Sentinel Initiative
d) Sentinel Initiative
Conducting Clinical Research
p 116
The __________ projects include: 1) reporting and interpreting serious adverse events and 2) improving monitoring practices.
a) Clinical Trials Transformation Initiative
b) ClinicalTrials.gov
c) Genetic Information Nondiscrimination Act
d) Sentinel Initiative
a) Clinical Trials Transformation Initiative
Conducting Clinical Research
p 117
The ___________ says that genetic information cannot be used to make decisions regarding health insurance underwriting or the hiring, firing, and promotion of employees. Research volunteers are informed more clearly about privacy risks regarding their genetic data.
a) Clinical Trials Transformation Initiative
b) ClinicalTrials.gov
c) Genetic Information Nondiscrimination Act
d) Sentinel Initiative
c) Genetic Information Nondiscrimination Act
Conducting Clinical Research
p 117
Non-U.S. study sites may be audited by the FDA.
true
false
true
…particularly if the application relies substantially on non-U.S. data, if major discrepancies between U.S. and non-U.S. data exist, or if fraud or abuse is suspected.
Conducting Clinical Research
p 118
A ___________ is a study performed in the new region to provide pharmacodynamic or clinical data on efficacy, safety, dosage and dose regimen in the new region that will allow extrapolation of the foreign clinical data to the population in the new region.
a) bridging study
b) ethnicity study
c) feasibility study
d) longitudinal study
a) bridging study
To overcome concerns about the use of data from different regions of the world, the ICH E5 provides guidelines regarding “Ethnic Factors in the Acceptability of Foreign Clinical Data.”
These are specifically required by Japanese regulatory agencies, for example, because significant differences in metabolism, dosing, and adverse reactions have been shown with a variety of drugs.
Conducting Clinical Research
p 118
The IRB must:
a) approve protocol, consent form, and advertisements prior to their use
b) review each protocol annually, at minimum
c) review all IND safety reports as well as trial outcomes at the study site and decide if any intervention is necessary
d) a and b
e) all of the above
e) all of the above
Conducting Clinical Research
p 123
IRBs may be commercial, centralized, and for-profit enterprises or nonprofit boards maintained by local hospitals or academic institutions.
true
false
true
Conducting Clinical Research
p 123
Significant equity interest in the sponsor of a covered study means:
any ownership interest, stock options, or other financial interest whose value cannot be readily determined through reference to public prices, or any equity interest in a publicly traded corporation that exceeds _________ during the time the clinical investigator is carrying out the study and for ______ following completion of the study.
a) $25,000; 1 year
b) $25,000; 2 years
c) $50,000; 1 year
d) $50,000; 2 years
c) $50,000; 1 year
21 CFR Part 54.2(b)
Significant payments of other sorts means:
payments made by the sponsor of a covered study to the investigator or the institution to support activities of the investigator that have a monetary value of more than ______, exclusive of the costs of conducting the clinical study or other clinical studies, during the time the clinical investigator is carrying out the study and for ______ following the completion of the study.
a) $25,000; 1 year
b) $25,000; 2 years
c) $50,000; 1 year
d) $50,000; 2 years
a) $25,000; 1 year
21 CFR Part 54.2(f)
Financial Disclosure by Clinical Investigators
Any potential conflicts must be disclosed. If financial benefits in excess of the limits on Form FDA ____ are in play, a different form, Form FDA ____, will need to be filed, detailing the financial arrangements between the investigator and sponsor.
3454; 3455
Conducting Clinical Research
p 131
A clinical study can undergo two kinds of audits, the in-house ones and the out-house ones.
true
false
true
in-house: conducted or contracted for by the sponsor
out-house: FDA audits
Conducting Clinical Research
p 132
When tasks are delegated by the investigator, the investigator is responsible for providing adequate supervision of those to whom tasks are delegated and the investigator is accountable for regulatory violations resulting from failure to adequately supervise the conduct of the clinical study.
true
false
true
Conducting Clinical Research
p 133
The FDA conducts two kinds of audits: those that are routine and those that are “for cause.”
true
false
true
routine: generally 3-10 days advance notice
Conducting Clinical Research
p 134
Form 483 is subclassified as follows:
NAI - no action indicated
VAI - voluntary action indicated
OAI - official action indicated
true
false
true
Conducting Clinical Research
p 140
A routine FDA audit inspects:
a) only specific study (i.e., SOP manual and regulatory binder, consents, safety reports)
b) contracts
c) grant material
a) only specific study
Conducting Clinical Research
p 142
Maintains ultimate responsibility for the implementation of the trial.
a) Sponsor
b) Investigator or Sponsor-Investigator
c) a and b
b) Investigators or Sponsor-Investigators
http: //ctsieducation.umn.edu/gcp/index.php
Responsible for the quality and integrity of the research.
a) Sponsor
b) Investigator or Sponsor-Investigator
c) a and b
a) Sponsor
http: //ctsieducation.umn.edu/gcp/index.php
Committee established by a sponsor to review trial data and make recommendations regarding the ongoing progress of the clinical trial.
a) Independent Data Monitoring Committee
b) Contract Research Organization
c) Medical Monitors
a) Independent Data Monitoring Committee
http: //ctsieducation.umn.edu/gcp/index.php
Person or organization hired by a sponsor to perform some of the sponsor’s trial-related duties.
a) Independent Data Monitoring Committee
b) Contract Research Organization
c) Medical Monitors
b) Contract Research Organization
http: //ctsieducation.umn.edu/gcp/index.php
Medical experts hired by sponsors to advise on trial-related medical questions or problems.
a) Independent Data Monitoring Committee
b) Contract Research Organization
c) Medical Monitors
c) Medical Monitors
http: //ctsieducation.umn.edu/gcp/index.php
What is the role of an independent data monitoring committee?
a) To assess how well an investigator has followed the protocol
b) To assess the progress of a study through review of safety and efficacy data
c) To assess the quality of the monitoring of a study
d) To monitor the number of adverse events occuring at each site in a study
b) To assess the progress of a study through review of safety and efficacy data
http: //ctsieducation.umn.edu/gcp/index.php
What is the purpose of clinical trial audits?
a) Checking for conflict of interest relationships
b) Checking the monitoring of the study
c) Monitoring the financial affairs at each study site
d) Monitoring quality control of investigational product handling at each study site
b) Checking the monitoring of the study
http: //ctsieducation.umn.edu/gcp/index.php
To fully comply with the ICH GCP guidelines, clinical research professionals must also carefully study the principles found in the Declaration of Helsinki.
true
false
true
http://ctsieducation.umn.edu/gcp/index.php
Only a qualified physician can decide upon the medical care provided to human subjects in clinical research.
true
false
false
a qualified dentist may also decide upon and be responsible for medical care in appropriate research studies
http://ctsieducation.umn.edu/gcp/index.php
