Other Reading

Question 1

What do usual measures of adverse effects include?

Answer 1

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

Question 2

What is the Common Rule?

Answer 2

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

Question 3

What is beneficense?

Answer 3

doing no harm, maximizing benefits while minimizing risks

Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick

Question 4

What is/are Kefauver-Harris Amendments?

Answer 4

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

Question 5

What are CIOMS guidelines?

Answer 5

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

Question 6

What is the PPRA?

Answer 6

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

Question 7

Title 21 CFR _____________
Title 45 CFR _____________

(fill in the blanks)

Answer 7

21: Food and Drugs
45: Public Welfare

Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick

Question 8

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

Answer 8

true

Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick

Question 9

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

Answer 9

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

Question 10

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

Answer 10

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

Question 11

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)

Answer 11

National Research Act

Protecting Study Volunteers in Research
A Manual for Investigative Sites
3rd edition
Dunn/Chadwick

Question 12

The Belmont Report
The principle of beneficence is applied in ___________.
(fill in the blank)

Answer 12

risk/benefit assessments

Question 13

The Belmont Report
The principle of justice is applied in the _____________.
(fill in the blank)

Answer 13

selection of research subjects

Question 14

The Belmont Report
The principle of respect for persons is applied in the _____________.
fill in the blank

Answer 14

consent process

Question 15

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

Answer 15

all

Question 16

What is FERPA?

Answer 16

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.

Question 17

What is PPRA?

Answer 17

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.

Question 18

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

Answer 18

a, b, and c

Question 19

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

Answer 19

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.

Question 20

______ 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)

Answer 20

coercion

undue influence

Question 21

Justice is relevant to the selection of subjects of research at which two levels?

Answer 21

social and individual

Question 22

What are the three main protective mechanisms established in the Common Rule?

Answer 22

1) review of research by an IRB
2) informed consent of subjects
3) institutional assurances of compliance

Protecting Study Volunteers in Research
p 37

Question 23

What is an FWA?

Answer 23

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

Question 24

What are the two main purposes of GCP?

Answer 24

1) to protect human subjects during clinical studies

2) to protect patients who might receive approved products in the future

Question 25

There is no one source of guidance for GCPs. true false

Answer 25

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

Question 26

Payments to research subjects is considered a benefit. true false

Answer 26

false It is a recruitment incentive.

Question 27

Exemption from IND/IDE regulations is an exemption from IRB review. true false

Answer 27

false Protecting Study Volunteers in Research p 63

Question 28

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

Answer 28

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.

Question 29

An FDA-approved IDE application is required prior to human subject exposure for all device studies. true false

Answer 29

false | ...for all significant-risk device studies

Question 30

There is no Form FDA 1572 for device studies. true false

Answer 30

true However, documentation of similar commitments by the investigators is required in either the IDE application or in the sponsor's contracts with investigators.

Question 31

Study Process for Industry-Sponsored Studies The investigator responsibilities critical to the conduct of industry-sponsored studies include which three additional processes?

Answer 31

1) investigational materials handling and accountability 2) adverse events 3) documentation

Question 32

What are DARs?

Answer 32

drug or device accountability records

Question 33

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

Answer 33

b) 10

Question 34

Investigators are advised to contact the study sponsor before any study related records are destroyed to ensure compliance with the regulatory requirements. true false

Answer 34

true

Question 35

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

Answer 35

true It is advisable, however, to call the FDA to confirm that they do not have any issues or concerns with the application.

Question 36

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

Answer 36

c) 15

Question 37

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)

Answer 37

5 15 so basically, evaluation must be conducted within 10 days max notification to termination is 15 days max

Question 38

What is a Certificate of Confidentiality?

Answer 38

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.

Question 39

All clinical gene transfer trials are subject to FDA regulations (21 CFR 312) as biological products. true false

Answer 39

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.

Question 40

Regarding gene transfer trials... The roles of the IBC (Institutional Biosafety Committee) and IRB overlap when considering human subjects protection. true false

Answer 40

true While many IBCs have minimal experience with clinical settings, many IRBs have little knowledge of the technical issues associated with the gene transfer.

Question 41

All clinical trials require safety monitoring, but not all trials require a DMC. true false

Answer 41

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???

Question 42

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

Answer 42

a) different from The HIPAA Privacy Rule affects any research use or disclosure of PHI.

Question 43

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

Answer 43

a, b, c, and d

Question 44

The Privacy Rule does not apply to de-identified data. true false

Answer 44

true

Question 45

In a __________ study, neither the participants nor the investigators responsible for following the participants know the identity of the intervention assignment.

Answer 45

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

Question 46

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.

Answer 46

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

Question 47

___________ 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 _________.

Answer 47

Randomized randomization Fundamentals of Clinical Trials Friedman pg 43

Question 48

______ 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.

Answer 48

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

Question 49

A properly planned and executed clinical trial is a powerful experimental technique for assessing the effectiveness of an intervention. true false

Answer 49

true Fundamentals of Clinical Trials Friedman pg 2

Question 50

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

Answer 50

true Fundamentals of Clinical Trials Friedman pg 30

Question 51

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

Answer 51

true Fundamentals of Clinical Trials Friedman pg 16

Question 52

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

Answer 52

true Fundamentals of Clinical Trials Friedman pg 42

Question 53

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

Answer 53

true Fundamentals of Clinical Trials Friedman pg 61

Question 54

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

Answer 54

false ...ideally, have a double-blind design... Fundamentals of Clinical Trials Friedman pg 82

Question 55

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

Answer 55

true Fundamentals of Clinical Trials Friedman pg 94

Question 56

Relevant baseline data should be measured in all study participants before the start of intervention. true false

Answer 56

true Fundamentals of Clinical Trials Friedman pg 130

Question 57

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

Answer 57

true Fundamentals of Clinical Trials Friedman pg 141

Question 58

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

Answer 58

false ...during all phases of a study... Fundamentals of Clinical Trials Friedman pg 157

Question 59

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

Answer 59

true Fundamentals of Clinical Trials Friedman pg 170

Question 60

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

Answer 60

true Fundamentals of Clinical Trials Friedman pg 186

Question 61

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

Answer 61

false ...adherence problems can be prevented... Fundamentals of Clinical Trials Friedman pg 205

Question 62

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

Answer 62

true Fundamentals of Clinical Trials Friedman pg 223

Question 63

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

Answer 63

true Fundamentals of Clinical Trials Friedman pg 246

Question 64

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

Answer 64

false ...response variables can lead to biased results... Fundamentals of Clinical Trials Friedman pg 284

Question 65

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

Answer 65

true Fundamentals of Clinical Trials Friedman pg 323

Question 66

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

Answer 66

false The investigators have an obligation... Fundamentals of Clinical Trials Friedman pg 334

Question 67

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

Answer 67

true Fundamentals of Clinical Trials Friedman pg 345

Question 68

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

Answer 68

b) protect the rights and welfare of human subjects of research The CRCs Guide to Coordinating Clinical Research

Question 69

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

Answer 69

b) before enrolling any patients in the study The CRCs Guide to Coordinating Clinical Research

Question 70

What is form FDA 2522?

Answer 70

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.

Question 71

An ___________________ is a research permit to allow an unapproved medical device to be tested on humans to evaluate safety and efficacy.

Answer 71

Investigational Device Exemption (IDE) Guide to Clinical Trials p 1011

Question 72

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.

Answer 72

Premarket Approval Application (PMA) Guide to Clinical Trials p 1011

Question 73

What is form FDA 356h?

Answer 73

Application to Market a New or Abbreviated New Drug or Biologic for Human Use Guide to Clinical Trials p 1010

Question 74

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).

Answer 74

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

Question 75

________________ 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).

Answer 75

Premarket Notification (510k) Guide to Clinical Trials p 1010

Question 76

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

Answer 76

a) written notification saying it has been approved The CRCs Guide to Coordinating Clinical Research

Question 77

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

Answer 77

d) the full protocol and the informed consent The CRCs Guide to Coordinating Clinical Research

Question 78

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

Answer 78

a) must be submitted to the RIB and approved before it can be used The CRCs Guide to Coordinating Clinical Research

Question 79

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

Answer 79

a) increases the risk to subjects The CRCs Guide to Coordinating Clinical Research

Question 80

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

Answer 80

f) all of the above The CRCs Guide to Coordinating Clinical Research

Question 81

The investigator's signature must be on the consent form. true false

Answer 81

false The CRCs Guide to Coordinating Clinical Research

Question 82

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

Answer 82

true Protecting Study Volunteers in Research p 138

Question 83

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

Answer 83

true Protecting Study Volunteers in Research p 63

Question 84

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

Answer 84

true Protecting Study Volunteers in Research p 67

Question 85

_______ documentation is where the information is first recorded, including medical records and case report forms.

Answer 85

Source Protecting Study Volunteers in Research p 70

Question 86

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

Answer 86

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

Question 87

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

Answer 87

b) 7 Protecting Study Volunteers in Research p 73

Question 88

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

Answer 88

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.

Question 89

The reporting requirements for adverse device effects are ___________ those for drugs and biologics. a) the same as b) similar to c) different from

Answer 89

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.

Question 90

The _________ is responsible for recommending trial termination when subject safety is jeopardized. a) investigator b) sponsor c) DMC d) monitor

Answer 90

c) DMC (data monitoring committee) Protecting Study Volunteers in Research p 137

Question 91

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

Answer 91

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

Question 92

An investigator’s brochure is required of sponsors, and recommended but not required of sponsor- investigators. true false

Answer 92

true http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM446695.pdf

Question 93

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

Answer 93

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

Question 94

The sponsor-investigator’s signature on Form FDA 1572 is a commitment to obtain IRB approval before initiating the trial. true false

Answer 94

true http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM446695.pdf

Question 95

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

Answer 95

true http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM446695.pdf

Question 96

Charging for the investigational drug is only permitted in rare circumstances, and then only with prior written approval by the FDA. true false

Answer 96

true http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM446695.pdf

Question 97

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

Answer 97

true http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM446695.pdf

Question 98

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

Answer 98

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

Question 99

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

Answer 99

a) Application to Market a New or Abbreviated New Drug or Biologic for Human Use

Question 100

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

Answer 100

c) Transmittal of Annual Reports for Drugs and Biologics for Human Use

Question 101

The Privacy Rule actually covers a broader scope of research activities than does the Common Rule. true false

Answer 101

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

Question 102

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

Answer 102

e) informed consent The CRCs Guide to Coordinating Clinical Research

Question 103

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

Answer 103

a) a written, signed and dated informed consent form The CRCs Guide to Coordinating Clinical Research

Question 104

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

Answer 104

b) the subject The CRCs Guide to Coordinating Clinical Research

Question 105

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

Answer 105

e) all of the above The CRCs Guide to Coordinating Clinical Research

Question 106

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

Answer 106

b) rights and well-being of study subjects and credibility of the data The CRCs Guide to Coordinating Clinical Research

Question 107

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

Answer 107

a) safety surveillance systems The CRCs Guide to Coordinating Clinical Research

Question 108

Non-clinical studies refer to studies that do not involve: a) animal testing b) drugs c) human subjects d) toxicolgy parameters e) safety

Answer 108

c) human subjects The CRCs Guide to Coordinating Clinical Research

Question 109

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

Answer 109

a) Phase I The CRCs Guide to Coordinating Clinical Research

Question 110

Large multicenter studies are usually done in: a) Phase I b) Phase II c) Phase III d) Phase IIIB e) Phase IV

Answer 110

c) Phase III The CRCs Guide to Coordinating Clinical Research

Question 111

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

Answer 111

c) demonstrate efficacy within the established safe dose range The CRCs Guide to Coordinating Clinical Research

Question 112

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

Answer 112

e) all of the above The CRCs Guide to Coordinating Clinical Research

Question 113

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

Answer 113

d) until the sponsor says they may be destroyed The CRCs Guide to Coordinating Clinical Research

Question 114

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

Answer 114

b) grant information The CRCs Guide to Coordinating Clinical Research

Question 115

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

Answer 115

c) data are first recorded The CRCs Guide to Coordinating Clinical Research

Question 116

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

Answer 116

e) all the above The CRCs Guide to Coordinating Clinical Research

Question 117

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

Answer 117

a) written descriptions of how tasks are to be performed The CRCs Guide to Coordinating Clinical Research

Question 118

Once an SOP is in place, it should never be changed. true false

Answer 118

false The CRCs Guide to Coordinating Clinical Research

Question 119

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

Answer 119

b) a study coordinator The CRCs Guide to Coordinating Clinical Research

Question 120

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

Answer 120

e) a, b, and c The CRCs Guide to Coordinating Clinical Research

Question 121

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?

Answer 121

a) will the sponsor pay at least 30% of the grant in advance? The CRCs Guide to Coordinating Clinical Research

Question 122

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

Answer 122

c) fee-for-service The CRCs Guide to Coordinating Clinical Research

Question 123

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

Answer 123

d) only those people listed on the 1572 The CRCs Guide to Coordinating Clinical Research

Question 124

Investigator meetings are a requirement for any multicenter study with six or more sites. true false

Answer 124

false The CRCs Guide to Coordinating Clinical Research

Question 125

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

Answer 125

b) after the site has received all study materials and is ready to start enrollment The CRCs Guide to Coordinating Clinical Research

Question 126

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

Answer 126

c) recruiting sufficient subjects The CRCs Guide to Coordinating Clinical Research

Question 127

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

Answer 127

a) part of the consent process The CRCs Guide to Coordinating Clinical Research

Question 128

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

Answer 128

c) be done only with prior IRB approval The CRCs Guide to Coordinating Clinical Research

Question 129

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

Answer 129

e) a, b, and c The CRCs Guide to Coordinating Clinical Research

Question 130

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

Answer 130

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

Question 131

Patient compliance with study drug dosing is a statistical issue, so site personnel do not have to be concerned about it. true false

Answer 131

false The CRCs Guide to Coordinating Clinical Research

Question 132

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

Answer 132

d) the amount of the grant per subject The CRCs Guide to Coordinating Clinical Research

Question 133

Case report forms are usually completed by: a) the investigator b) the CRC c) the CRA d) the subject e) the sponsor

Answer 133

b) the CRC The CRCs Guide to Coordinating Clinical Research

Question 134

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

Answer 134

c) the CRC or the investigator The CRCs Guide to Coordinating Clinical Research

Question 135

It is a regulatory requirement to have a source document for every data item collected on case report forms. true false

Answer 135

false The CRCs Guide to Coordinating Clinical Research

Question 136

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

Answer 136

a) the study is complete The CRCs Guide to Coordinating Clinical Research

Question 137

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

Answer 137

b) the sponsor and the IRB The CRCs Guide to Coordinating Clinical Research

Question 138

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

Answer 138

e) b and c The CRCs Guide to Coordinating Clinical Research

Question 139

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

Answer 139

a) does not have routine access to The CRCs Guide to Coordinating Clinical Research

Question 140

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

Answer 140

c) to determine that the drug was properly manufactured The CRCs Guide to Coordinating Clinical Research

Question 141

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

Answer 141

d) closed The CRCs Guide to Coordinating Clinical Research

Question 142

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

Answer 142

a) study conduct and study data The CRCs Guide to Coordinating Clinical Research

Question 143

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.

Answer 143

a) VAI. The CRCs Guide to Coordinating Clinical Research

Question 144

____ 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

Answer 144

a) Class I | http: //www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf

Question 145

_____ 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

Answer 145

b) Class II | http: //www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf

Question 146

_____ 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

Answer 146

c) Class III | http: //www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf

Question 147

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

Answer 147

c) 4,000 | http: //www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf

Question 148

Humanitarian Use Devices a) 21 CFR Part 314 b) 21 CFR Part 505 c) 21 CFR Part 600 d) 21 CFR Part 814

Answer 148

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

Question 149

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

Answer 149

true http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf

Question 150

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

Answer 150

true http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf

Question 151

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

Answer 151

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

Question 152

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

Answer 152

true http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf

Question 153

The act and the HDE regulations require informed consent when treating/diagnosing a patient with an HUD. true false

Answer 153

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

Question 154

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

Answer 154

true http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf

Question 155

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

Answer 155

a, b, c, d, e, f, g http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126555.pdf

Question 156

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

Answer 156

true http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126555.pdf

Question 157

FDA’s inspection of clinical investigators is limited to the United States true false

Answer 157

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

Question 158

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.

Answer 158

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

Question 159

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

Answer 159

d) the investigator and, where appropriate, the sponsor | http: //socra.wcea.education/searchOnlineTraining#/training/133162

Question 160

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

Answer 160

true http://en.wikipedia.org/wiki/Covered_clinical_study

Question 161

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

Answer 161

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

Question 162

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.

Answer 162

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

Question 163

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.

Answer 163

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

Question 164

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.

Answer 164

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

Question 165

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.

Answer 165

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

Question 166

The Federal government implemented the Health Insurance Portability and Accountability Act (HIIPAA) Privacy Rule in: a) 1991 b) 1998 c) 2003 d) 2008

Answer 166

c) 2003 The CRC's Guide to Coordinating Clinical Research p 39

Question 167

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

Answer 167

c) 45 CFR Parts 160 and 164 The CRC's Guide to Coordinating Clinical Research p 39

Question 168

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

Answer 168

a) emergency use http: //www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/ucm051345.htm#top

Question 169

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

Answer 169

b) emergency research http: //www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/ucm051345.htm#top

Question 170

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

Answer 170

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

Question 171

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

Answer 171

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

Question 172

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

Answer 172

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

Question 173

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

Answer 173

true http://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/ucm20080392.htm#Expanded_Access_Requirements

Question 174

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

Answer 174

true http://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/ucm20080392.htm#Expanded_Access_Requirements

Question 175

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

Answer 175

true Conducting Clinical Research p 12

Question 176

________ 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

Answer 176

c) Phase 3 Conducting Clinical Research p 13

Question 177

______ studies are sometimes referred to as postmarketing studies or commitment studies. a) Phase 1 b) Phase 2 c) Phase 3 d) Phase 4

Answer 177

d) Phase 4 Conducting Clinical Research p 13

Question 178

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

Answer 178

true Conducting Clinical Research p 13

Question 179

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

Answer 179

a) parallel study Conducting Clinical Research p 20

Question 180

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

Answer 180

d) crossover study Conducting Clinical Research p 20

Question 181

__________ 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

Answer 181

b) double-dummy protocol Conducting Clinical Research p 20

Question 182

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

Answer 182

c) open label study aka unblinded Conducting Clinical Research p 21

Question 183

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

Answer 183

d) single-blind study Conducting Clinical Research p 21

Question 184

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

Answer 184

e) double-blind study Conducting Clinical Research p 21

Question 185

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

Answer 185

true Conducting Clinical Research p 23

Question 186

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

Answer 186

true Conducting Clinical Research p 24

Question 187

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

Answer 187

true Conducting Clinical Research p 24

Question 188

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

Answer 188

true Conducting Clinical Research p 25

Question 189

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

Answer 189

true Conducting Clinical Research p 27

Question 190

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

Answer 190

d) Sentinel Initiative Conducting Clinical Research p 116

Question 191

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

Answer 191

a) Clinical Trials Transformation Initiative Conducting Clinical Research p 117

Question 192

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

Answer 192

c) Genetic Information Nondiscrimination Act Conducting Clinical Research p 117

Question 193

Non-U.S. study sites may be audited by the FDA. true false

Answer 193

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

Question 194

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

Answer 194

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

Question 195

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

Answer 195

e) all of the above Conducting Clinical Research p 123

Question 196

IRBs may be commercial, centralized, and for-profit enterprises or nonprofit boards maintained by local hospitals or academic institutions. true false

Answer 196

true Conducting Clinical Research p 123

Question 197

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

Answer 197

c) $50,000; 1 year 21 CFR Part 54.2(b)

Question 198

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

Answer 198

a) $25,000; 1 year 21 CFR Part 54.2(f)

Question 199

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.

Answer 199

3454; 3455 Conducting Clinical Research p 131

Question 200

A clinical study can undergo two kinds of audits, the in-house ones and the out-house ones. true false

Answer 200

true in-house: conducted or contracted for by the sponsor out-house: FDA audits Conducting Clinical Research p 132

Question 201

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

Answer 201

true Conducting Clinical Research p 133

Question 202

The FDA conducts two kinds of audits: those that are routine and those that are "for cause." true false

Answer 202

true routine: generally 3-10 days advance notice Conducting Clinical Research p 134

Question 203

Form 483 is subclassified as follows: NAI - no action indicated VAI - voluntary action indicated OAI - official action indicated true false

Answer 203

true Conducting Clinical Research p 140

Question 204

A routine FDA audit inspects: a) only specific study (i.e., SOP manual and regulatory binder, consents, safety reports) b) contracts c) grant material

Answer 204

a) only specific study Conducting Clinical Research p 142

Question 205

Maintains ultimate responsibility for the implementation of the trial. a) Sponsor b) Investigator or Sponsor-Investigator c) a and b

Answer 205

b) Investigators or Sponsor-Investigators | http: //ctsieducation.umn.edu/gcp/index.php

Question 206

Responsible for the quality and integrity of the research. a) Sponsor b) Investigator or Sponsor-Investigator c) a and b

Answer 206

a) Sponsor | http: //ctsieducation.umn.edu/gcp/index.php

Question 207

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

Answer 207

a) Independent Data Monitoring Committee | http: //ctsieducation.umn.edu/gcp/index.php

Question 208

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

Answer 208

b) Contract Research Organization | http: //ctsieducation.umn.edu/gcp/index.php

Question 209

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

Answer 209

c) Medical Monitors | http: //ctsieducation.umn.edu/gcp/index.php

Question 210

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

Answer 210

b) To assess the progress of a study through review of safety and efficacy data http: //ctsieducation.umn.edu/gcp/index.php

Question 211

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

Answer 211

b) Checking the monitoring of the study | http: //ctsieducation.umn.edu/gcp/index.php

Question 212

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

Answer 212

true http://ctsieducation.umn.edu/gcp/index.php

Question 213

Only a qualified physician can decide upon the medical care provided to human subjects in clinical research. true false

Answer 213

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