SOCRA Exam Prep

Question 1

A sponsor shall retain the records and reports required by this part for [___] years after a marketing application is approved for the drug; or, if an application is not approved for the drug, until [___] years after shipment and delivery of the drug for investigational use is discontinued and FDA has been so notified.

Answer 1

2,2

Question 2

A sponsor may request FDA to waive applicable requirement under this part. A waiver request may be submitted either in an IND or in an information amendment to an IND. In an emergency, a request may be made by telephone or other rapid communication means. A waiver request is required to contain at least one of the following:

Answer 2

(1) An explanation why the sponsor’s compliance with the requirement is unnecessary or cannot be achieved;

(2) A description of an alternative submission or course of action that satisfies the purpose of the requirement; or

(3) Other information justifying a waiver.

Question 3

Phase [___] includes the initial introduction of an investigational new drug into humans. These studies are typically closely monitored and may be conducted in patients or normal volunteer subjects. These studies are designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.

Answer 3

Phase 1

Question 4

Phase [___] includes the controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks associated with the drug. These studies are typically well controlled, closely monitored, and conducted in a relatively small number of patients, usually involving no more than several hundred subjects.

Answer 4

Phase 2

Question 5

Phase [___] studies are expanded controlled and uncontrolled trials. They are performed after preliminary evidence suggesting effectiveness of the drug has been obtained, and are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling. These studies usually include from several hundred to several thousand subjects.

Answer 5

Phase 3

Question 6

A protocol is required to contain the following, with the specific elements and detail of the protocol reflecting the above distinctions depending on the phase of study:

Answer 6

(a) A statement of the objectives and purpose of the study.

(b) The name and address and a statement of the qualifications (curriculum vitae or other statement of qualifications) of each investigator, and the name of each subinvestigator (e.g., research fellow, resident) working under the supervision of the investigator; the name and address of the research facilities to be used; and the name and address of each reviewing Institutional Review Board.

(c) The criteria for patient selection and for exclusion of patients and an estimate of the number of patients to be studied.

(d) A description of the design of the study, including the kind of control group to be used, if any, and a description of methods to be used to minimize bias on the part of subjects, investigators, and analysts.

(e) The method for determining the dose(s) to be administered, the planned maximum dosage, and the duration of individual patient exposure to the drug.

(f) A description of the observations and measurements to be made to fulfill the objectives of the study.

(g) A description of clinical procedures, laboratory tests, or other measures to be taken to monitor the effects of the drug in human subjects and to minimize risk.

Question 7

New protocol. Whenever a sponsor intends to conduct a study that is not covered by a protocol already contained in the IND, the sponsor shall submit to FDA a protocol amendment containing the protocol for the study. Such study may begin provided two conditions are met:

Answer 7

(1) The sponsor has submitted the protocol to FDA for its review; and

(2) the protocol has been approved by the Institutional Review Board (IRB) with responsibility for review and approval of the study in accordance with the requirements of part 56. The sponsor may comply with these two conditions in either order.

Question 8

A sponsor shall submit a protocol amendment describing any change in a Phase 1 protocol that significantly affects the safety of subjects or any change in a Phase 2 or 3 protocol that significantly affects the safety of subjects, the scope of the investigation, or the scientific quality of the study. Examples of changes requiring an amendment under this paragraph include:

Answer 8

(i) Any increase in drug dosage or duration of exposure of individual subjects to the drug beyond that in the current protocol, or any significant increase in the number of subjects under study.

(ii) Any significant change in the design of a protocol (such as the addition or dropping of a control group).

(iii) The addition of a new test or procedure that is intended to improve monitoring for, or reduce the risk of, a side effect or adverse event; or the dropping of a test intended to monitor safety.

Question 9

What is a Life-threatening adverse event or life-threatening suspected adverse reaction?

Answer 9

An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of death. It does not include an adverse event or suspected adverse reaction that, had it occurred in a more severe form, might have caused death.

Question 10

What is a Serious adverse event or serious suspected adverse reaction?

Answer 10

An adverse event or suspected adverse reaction is considered “serious” if, in the view of either the investigator or sponsor, it results in any of the following outcomes:
Death,
a life-threatening adverse event,
inpatient hospitalization or
prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.

Question 11

What is a Suspected adverse reaction?

Answer 11

means any adverse event for which there is a reasonable possibility that the drug caused the adverse event. For the purposes of IND safety reporting, “reasonable possibility” means there is evidence to suggest a causal relationship between the drug and the adverse event. Suspected adverse reaction implies a lesser degree of certainty about causality than adverse reaction, which means any adverse event caused by a drug.

Question 12

What is an Unexpected adverse event or unexpected suspected adverse reaction?

Answer 12

An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in the investigator brochure or is not listed at the specificity or severity that has been observed; or, if an investigator brochure is not required or available, is not consistent with the risk information described in the general investigational plan or elsewhere in the current application, as amended.

For example, under this definition, hepatic necrosis would be unexpected (by virtue of greater severity) if the investigator brochure referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) if the investigator brochure listed only cerebral vascular accidents. “Unexpected,” as used in this definition, also refers to adverse events or suspected adverse reactions that are mentioned in the investigator brochure as occurring with a class of drugs or as anticipated from the pharmacological properties of the drug, but are not specifically mentioned as occurring with the particular drug under investigation.

Question 13

The sponsor must notify FDA and all participating investigators (i.e., all investigators to whom the sponsor is providing drug under its INDs or under any investigator’s IND) in an IND safety report of potential serious risks, from clinical trials or any other source, as soon as possible, but in no case later than [___] calendar days after the sponsor determines that the information qualifies for reporting under.

Answer 13

15 calendar days

Question 14

Unexpected fatal or life-threatening suspected adverse reaction reports. The sponsor must also notify FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible but in no case later than [___] calendar days after the sponsor’s initial receipt of the information.

Answer 14

7 calendar days

Question 15

A sponsor shall within [___] days of the anniversary date that the IND went into effect, submit a brief annual report of the progress of the investigation.

Answer 15

60 days

Question 16

A sponsor shall retain the records and reports required by this part for [___] years after a marketing application is approved for the drug; or, if an application is not approved for the drug, until [___] years after shipment and delivery of the drug for investigational use is discontinued and FDA has been so notified.

Answer 16

2 years, 2 years

Question 17

An investigator shall retain records required to be maintained under this part for a period of [___] years following the date a marketing application is approved for the drug for the indication for which it is being investigated; or, if no application is to be filed or if the application is not approved for such indication, until [___] years after the investigation is discontinued and FDA is notified.

Answer 17

2 years, 2 years

Question 18

The clinical investigator shall provide the sponsor with sufficient accurate financial information to allow an applicant to submit complete and accurate certification or disclosure statements as required under 21 CFR 312 Part 54 of. The clinical investigator shall promptly update this information if any relevant changes occur during the course of the investigation and for [___] year following the completion of the study.

Answer 18

1 year

Question 19

Abbreviated Requirements:
The following categories of investigations are considered to have approved applications for IDE’s, unless FDA has notified a sponsor under § 812.20(a) that approval of an application is required:

Answer 19

(1) An investigation of a device other than a significant risk device, if the device is not a banned device and the sponsor:

(i) Labels the device in accordance with § 812.5;

(ii) Obtains IRB approval of the investigation after presenting the reviewing IRB with a brief explanation of why the device is not a significant risk device, and maintains such approval;

(iii) Ensures that each investigator participating in an investigation of the device obtains from each subject under the investigator’s care, informed consent in accordance with part 50 of this chapter.

(iv) Complies with the requirements of § 812.46 with respect to monitoring investigations;

(v) Maintains the records required under § 812.140(b) (4) and (5) and makes the reports required under § 812.150(b) (1) through (3) and (5) through (10);

(vi) Ensures that participating investigators maintain the records required by § 812.140(a)(3)(i) and make the reports required under § 812.150(a) (1), (2), (5), and (7); and

(vii) Complies with the prohibitions in § 812.7 against promotion and other practices.

(2) An investigation of a device other than one subject to paragraph (e) of this section, if the investigation was begun on or before July 16, 1980, and to be completed, and is completed, on or before January 19, 1981.

Question 20

Exempted investigations. This part, with the exception of § 812.119, does not apply to investigations of the following categories of devices:

Answer 20

(1) A device, other than a transitional device, in commercial distribution immediately before May 28, 1976, when used or investigated in accordance with the indications in labeling in effect at that time.

(2) A device, other than a transitional device, introduced into commercial distribution on or after May 28, 1976, that FDA has determined to be substantially equivalent to a device in commercial distribution immediately before May 28, 1976, and that is used or investigated in accordance with the indications in the labeling FDA reviewed under subpart E of part 807 in determining substantial equivalence.

(3) A diagnostic device, if the sponsor complies with applicable requirements in § 809.10(c) and if the testing:

(i) Is noninvasive,

(ii) Does not require an invasive sampling procedure that presents significant risk,

(iii) Does not by design or intention introduce energy into a subject, and

(iv) Is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure.

(4) A device undergoing consumer preference testing, testing of a modification, or testing of a combination of two or more devices in commercial distribution, if the testing is not for the purpose of determining safety or effectiveness and does not put subjects at risk.

(5) A device intended solely for veterinary use.

(6) A device shipped solely for research on or with laboratory animals and labeled in accordance with § 812.5(c).

(7) A custom device as defined in § 812.3(b), unless the device is being used to determine safety or effectiveness for commercial distribution.

Question 21

Significant risk device means an investigational device that:

Answer 21

(1) Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;

(2) Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;

(3) Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or

(4) Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.

Question 22

The investigational plan shall include, in the following order:

Answer 22

(a) Purpose. The name and intended use of the device and the objectives and duration of the investigation.

(b) Protocol. A written protocol describing the methodology to be used and an analysis of the protocol demonstrating that the investigation is scientifically sound.

(c) Risk analysis. A description and analysis of all increased risks to which subjects will be exposed by the investigation; the manner in which these risks will be minimized; a justification for the investigation; and a description of the patient population, including the number, age, sex, and condition.

(d) Description of device. A description of each important component, ingredient, property, and principle of operation of the device and of each anticipated change in the device during the course of the investigation.

(e) Monitoring procedures. The sponsor’s written procedures for monitoring the investigation and the name and address of any monitor.

(f) Labeling. Copies of all labeling for the device.

(g) Consent materials. Copies of all forms and informational materials to be provided to subjects to obtain informed consent.

(h) IRB information. A list of the names, locations, and chairpersons of all IRB’s that have been or will be asked to review the investigation, and a certification of any action taken by any of those IRB’s with respect to the investigation.

(i) Other institutions. The name and address of each institution at which a part of the investigation may be conducted that has not been identified in paragraph (h) of this section.

(j) Additional records and reports. A description of records and reports that will be maintained on the investigation in addition to those prescribed in subpart G.

Question 23

The sponsor of a treatment IDE shall submit progress reports on a [___] basis to all reviewing IRB’s and FDA until the filing of a marketing application.

Answer 23

Semi-annual

Question 24

Retention period. An investigator or sponsor shall maintain the records required by this subpart during the investigation and for a period of [___] years after the latter of the following two dates: The date on which the investigation is terminated or completed, or the date that the records are no longer required for purposes of supporting a premarket approval application, a notice of completion of a product development protocol, a humanitarian device exemption application, a premarket notification submission, or a request for De Novo classification.

Answer 24

2 years

Question 25

Which countries are part of the ICH?

Answer 25

The ICH MC has permanent representatives from the six Founding Members (EC, Europe; EFPIA; FDA, United States; JPMA; MHLW/PMDA, Japan; PhRMA), Standing Regulatory Members (Health Canada, Canada; Swissmedic, Switzerland).

Question 26

How many patients do you expect to enroll in a phase 2 study?

Answer 26

Phase II studies determine the effectiveness of an experimental drug on a particular disease or condition in approximately 100 to 300 volunteers. This phase may last from several months to two years.

Question 27

An investigator shall notify the sponsor and the reviewing IRB of any deviation from the investigational plan to protect the life or physical well-being of a subject in an emergency. Such notice shall be given as soon as possible, but in no event later than [___] working days after the emergency occurred. Except in such an emergency, prior approval by the sponsor is required for changes in or deviations from a plan, and if these changes or deviations may affect the scientific soundness of the plan or the rights, safety, or welfare of human subjects, FDA and IRB in accordance with § 812.35(a) also is required.

Answer 27

5 working days

Question 28

Unanticipated adverse device effects. A sponsor who conducts an evaluation of an unanticipated adverse device effect under § 812.46(b) shall report the results of such evaluation to FDA and to all reviewing IRB’s and participating investigators within [___] working days after the sponsor first receives notice of the effect. Thereafter the sponsor shall submit such additional reports concerning the effect as FDA requests.

Answer 28

10 working days

Question 29

Withdrawal of IRB approval. A sponsor shall notify FDA and all reviewing IRB’s and participating investigators of any withdrawal of approval of an investigation or a part of an investigation by a reviewing IRB within [___] working days after receipt of the withdrawal of approval.

Answer 29

5 working days

Question 30

Withdrawal of FDA approval. A sponsor shall notify all reviewing IRB’s and participating investigators of any withdrawal of FDA approval of the investigation, and shall do so within [___] working days after receipt of notice of the withdrawal of approval.

Answer 30

5 working days

Question 31

Recall and device disposition. A sponsor shall notify FDA and all reviewing IRB’s of any request that an investigator return, repair, or otherwise dispose of any units of a device. Such notice shall occur within [___] working days after the request is made and shall state why the request was made.

Answer 31

30 working days

Question 32

Final report. In the case of a significant risk device, the sponsor shall notify FDA within [___] working days of the completion or termination of the investigation and shall submit a final report to FDA and all reviewing the IRB’s and participating investigators within [___] months after completion or termination.

Answer 32

30 working days, 6 months

Question 33

Final Report. In the case of a device that is not a significant risk device, the sponsor shall submit a final report to all reviewing IRB’s within [___] months after termination or completion.

Answer 33

6 months

Question 34

Significant risk device determinations. If an IRB determines that a device is a significant risk device, and the sponsor had proposed that the IRB consider the device not to be a significant risk device, the sponsor shall submit to FDA a report of the IRB’s determination within [___] working days after the sponsor first learns of the IRB’s determination.

Answer 34

5 working days

Question 35

_________ means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

Answer 35

Minimal risk

Question 36

IRB Membership
Each IRB shall have at least [___] members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution. The IRB shall be sufficiently qualified through the experience and expertise of its members, and the diversity of the members, including consideration of race, gender, cultural backgrounds, and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects.

Answer 36

five (5) members

Question 37

Each IRB shall include at least [___] member whose primary concerns are in the scientific area and at least [___] member whose primary concerns are in nonscientific areas.

Answer 37

one, one

Question 38

What is an IRB?

Answer 38

Any board, committee, or other group formally designated by an institution to review, to approve the initiation of, and to conduct periodic review of, biomedical research involving human subjects. The primary purpose of such review is to assure the protection of the rights and welfare of the human subjects. (21 CFR 56.102(g) and 45 CFR 46.102(g))

Question 39

Meeting Quorum:
Majority must be present (including at least [___] member whose primary concern is nonscientific)

Answer 39

one member
Note: minimum composition requires 5 members, majority present (quorum) is at least 3 members, which means that with a majority vote that only 2 of 3 members are required for a decision from the IRB full board meetings

Question 40

Research that involves children must:

Answer 40

(1) Present no greater than minimal risk (only one parent/LAR need sign ICF)

(2) Have a prospect of direct benefit to the child if it is greater than minimal risk (only one parent/LAR need sign ICF). The risk must be justified by the benefits

(3) Yield generalizable knowledge about the child’s disorder/condition if greater than minimal risk and no prospect of direct benefit (both parents/LARs must sign). Must only be a minor increase over minimal risk, experiences must be reasonable to the disorder/condition

(4) Present an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children if not otherwise approval

Question 41

IRB Record Keeping Requirements
Maintain documentation of activities for [___] years post-completion of study, i.e., IRB closeout

Answer 41

3 years

Question 42

An IRB may use the expedited review procedure to review either or both of the following:

Answer 42

(1) Some or all of the research appearing on the list and found by the reviewer(s) to involve no more than minimal risk,

(2) minor changes in previously approved research during the period (of 1 year or less) for which approval is authorized. Under an expedited review procedure, the review may be carried out by the IRB chairperson or by one or more experienced reviewers designated by the IRB chairperson from among the members of the IRB. In reviewing the research, the reviewers may exercise all of the authorities of the IRB except that the reviewers may not disapprove the research. A research activity may be disapproved only after review in accordance with the nonexpedited review procedure set forth in § 56.108(c).

Question 43

Exception from informed consent requirements for minimal risk clinical investigations.

The IRB responsible for the review, approval, and continuing review of the clinical investigation described in this section may approve an informed consent procedure that does not include or that alters some or all of the elements of informed consent set forth in § 50.25(a) and (b), or may waive the requirement to obtain informed consent, provided the IRB finds and documents the following:

Answer 43

(a) The clinical investigation involves no more than minimal risk to the subjects;

(b) The clinical investigation could not practicably be carried out without the requested waiver or alteration;

(c) If the clinical investigation involves using identifiable private information or identifiable biospecimens, the clinical investigation could not practicably be carried out without using such information or biospecimens in an identifiable format;

(d) The waiver or alteration will not adversely affect the rights and welfare of the subjects; and

(e) Whenever appropriate, the subjects or legally authorized representatives will be provided with additional pertinent information after participation.

Question 44

Exception from general requirements
If immediate use of the test article is, in the investigator’s opinion, required to preserve the life of the subject, and time is not sufficient to obtain the independent determination required in advance of using the test article, the determinations of the clinical investigator shall be made and, within [___] working days after the use of the article, be reviewed and evaluated in writing by a physician who is not participating in the clinical investigation.

Answer 44

5 working days

Question 45

Basic elements of informed consent. In seeking informed consent, the following information shall be provided to each subject:

Answer 45

(1) 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.

(2) A description of any reasonably foreseeable risks or discomforts to the subject.

(3) A description of any benefits to the subject or to others which may reasonably be expected from the research.

(4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject.

(5) A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained and that notes the possibility that the Food and Drug Administration may inspect the records.

(6) For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained.

(7) An explanation of whom to contact for answers to pertinent questions about the research and research subjects’ rights, and whom to contact in the event of a research-related injury to the subject.

(8) 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.

Question 46

A [____] written consent document stating that the elements of informed consent required by § 50.25 have been presented orally to the subject or the subject’s legally authorized representative.

Answer 46

short form

Question 47

When the short form method is used, there shall be a [___] to the oral presentation.

Answer 47

witness

Question 48

When a short form is used, the IRB shall approve a [____] of what is to be said to the subject or the representative.

Answer 48

written summary

Question 49

Only the [___] itself is to be signed by the subject or the representative.

Answer 49

short form

Question 50

When a short form is used, the witness shall sign both the [____] and a copy of the [___], and the person actually obtaining the consent shall sign a copy of the [___]. A copy of the summary shall be given to the subject or the representative in addition to a copy of the short form.

Answer 50

short form, summary, summary

Question 51

IDE Abbreviated Requirements - Nonsignificant Risk

Answer 51

Unless your study, or your research is exempt from the investigational device exemption, then the study must comply with at least part of 812.

Nonsignificant risk devices do not pose significant health risk to patients and do not require an IDE application to FDA. They are subject to abbreviated IDE regulations and must be approved by an institutional review board (IRB). These requirements address labeling, IRB approval, informed consent, monitoring, records, and reports.* IRB serves as FDA’s surrogate for review, approval, and continuing review

Question 52

Studies that are only collecting data on device use (questionnaires, how people like the device, etc.) do not require an IDE and are considered [___]

Answer 52

exempt
Human subjects research that is classified as “exempt” means that the research qualifies as no risk or minimal risk to subjects and is exempt from most of the requirements of the Federal Policy for the Protection of Human Subjects, but is still considered research requiring an IRB review for an exemption determination.

Question 53

True/False
Under device regulations, the FDA grant certain authority of oversight to the IRB on their behalf.

Answer 53

True
This is important for studies that are not significant risk, because these do not require an application for an IDE, but they have certain abbreviated requirements. The FDA says to follow your IRBs guidance.

Question 54

Do IDE regulations apply if the device has already been approved for a different indication for use?

Answer 54

Yes, the clinical study of a new indication for an already marketed device falls under the IDE regulations.

Question 55

Who Decides Whether A Device Study is SR or NSR?

Answer 55

Sponsors are responsible for making the initial risk determination and presenting it to the IRB.

FDA is also available to help the sponsor, clinical investigator, and IRB in making the risk determination. The FDA is the final arbiter in deciding whether a device study poses a significant or nonsignificant risk. It should be noted, however, that FDA generally only sees those
studies that sponsors submit to the agency or those studies for which an IRB or clinical investigator asks for FDA’s opinion.

Question 56

Device studies that must follow all the IDE regulations at 21 CFR 812 and must have an IDE application approved by FDA before they may proceed.

Answer 56

Significant Risk Device Study

Question 57

Device studies that must follow the abbreviated requirements at 21 CFR 812.2(b).

These abbreviated requirements address labeling, IRB approval, informed consent, monitoring, records, reports, and prohibition against promotion. However, there is no need to make progress reports or final reports to FDA.

These studies do not have to have an IDE application approved by FDA, Sponsors and IRBs do not have to report the IRB approval to FDA. This means that an IRB may approve the study and an investigator may conduct the study without FDA knowing about it.

Note: An IRB’s determination is important because the IRB serves as the FDA’s surrogate for review, approval, and continuing review of the studies. The study may start at the institution as soon as the IRB reviews and approves the study and without prior approval by FDA.

Answer 57

Nonsignificant Risk Device Study

Question 58

WHAT SHOULD AN IRB DO FOR DEVICE STUDIES THAT ARE EXEMPT
FROM THE REQUIREMENTS OF THE IDE REGULATIONS (21 CFR
812.2(C))

Answer 58

For studies that are exempt from the IDE regulations, the IRB does not need to decide whether the study poses a significant risk or nonsignificant risk. However, the IRB must still review the
study in accordance with the IRB regulations before the investigation may begin. IRBs should understand distinctions between certain important concepts that are frequently confused.

Question 59

What is the difference between NSR and Minimal Risk Determinations?

Answer 59

“Minimal Risk” is a term used in the IRB regulations in part to identify certain studies that IRBs may approve through an expedited
review procedure. For a device study to be eligible for expedited review, it must be an NSR study AND present no more than minimal risk to the subject. (See 21 CFR 56.110)

Question 60

What does exempt mean?

Answer 60

Human subjects research that is classified as “exempt” means that the research qualifies as no risk or minimal risk to subjects and is exempt from most of the requirements of the Federal Policy for the Protection of Human Subjects, but is still considered research requiring an IRB review for an exemption determination.

Question 61

True/False
The FDA requires that data from clinical investigations conducted outside the US that began on or after February 21, 2019, be from investigations conducted in accordance with good clinical practice (GCP), which includes review and approval by an independent ethics committee (IEC) and informed consent from subjects.

Answer 61

True

Question 62

For clinical investigations intended to support an IDE or device marketing application or submission, the following statements and information must be included for each investigation:

Answer 62

Investigations conducted within the US:
Statement that the investigation was conducted in compliance with applicable requirements in the Protection of Human Subjects regulations in 21 CFR part 50, the Institutional Review Boards regulations in 21 CFR part 56, and the Investigational Device Exemptions regulations in 21 CFR part 812; or Statement describing the reasons for noncompliance.

Investigations conducted OUS:
The provisions under 21 CFR 812.28 apply. Specifically, the following must be included for each OUS clinical investigation:

Statement that each investigation was conducted in accordance with GCP as described in 21 CFR 812.28(a)(1);
Supporting information specified under 21 CFR 812.28(b), as specified in 21 CFR 812.28(a)(2), or a cross-reference to another section of the application or submission where the information is located.

Question 63

True/False
The FDA amended its regulations on the acceptance of data from clinical investigations for medical devices. Under the new rule, FDA is requiring that data submitted from clinical investigations conducted outside of the United States (OUS) intended to support an investigational device exemption (IDE) application, a premarket notification (510(k)) submission, a request for De Novo classification, a premarket approval (PMA) application, a humanitarian device exemption (HDE) application, or a product development protocol (PDP) application, be from investigations conducted in accordance with good clinical practice (GCP), which includes review and approval by an independent ethics committee (IEC) and informed consent from subjects.

Answer 63

True

Question 64

Who is responsible for the IND?

Answer 64

The sponsor of an IND is the individual, company, academic institution, or other organization that takes responsibility for and initiates the clinical investigation. The sponsor submits the IND to the FDA.

Question 65

Who is responsible for reporting safety issues to the FDA, IRB, etc.?

Answer 65

The sponsor

Question 66

Which signatures are required by FDA regulation to be on the consent form?

Answer 66

the participant

Question 67

In general, an AE observed during the conduct of a study should be considered an unanticipated problem involving risk to human subjects, and reported to the IRB, only if it were _________.

Answer 67

serious and would have serious implications for the conduct of the study

Question 68

True/False
Minimal risk is defined as “the magnitude of harm that a subject would encounter is not exceeded by those ordinarily encountered in daily life”.

Answer 68

True
The statement is true because minimal risk refers to the level of harm that a subject may encounter during a study, and this harm should not exceed the risks that individuals typically face in their everyday lives. In other words, the potential harm to participants should be no greater than what they would normally encounter in their daily activities. This ensures that the study does not pose an excessive risk to the participants’ well-being.

Question 69

True/False
The objective of the ICH GCP Guideline is to provide a unified standard for the European Union (EU), Japan, and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions.

Answer 69

True
The ICH GCP Guideline aims to establish a common standard for clinical data acceptance by regulatory authorities in the EU, Japan, and the United States. By providing a unified framework, it facilitates the mutual recognition and acceptance of clinical data across these jurisdictions. This helps streamline the regulatory process, ensuring that clinical trials conducted in these regions meet consistent quality standards and can be relied upon for decision-making purposes. Therefore, the statement “True” accurately reflects the objective of the ICH GCP Guideline.

Question 70

The contents of a Protocol should generally contain:

Answer 70

The contents of a protocol should generally include the trial objectives and purpose, assessment of efficacy, and data handling and record keeping.

Including the trial objectives and purpose helps to clearly define the goals and intentions of the study. Assessment of efficacy is crucial in determining the effectiveness of the intervention being studied. Data handling and record keeping ensure that all data collected during the trial is properly documented and organized for analysis. Therefore, all of the above options are necessary components of a protocol.

Question 71

True/False
When a short form is used for Informed Consent, the witness must sign either the short form or the summary.

Answer 71

According to regulations and best practices, the witness must sign both the short form and the summary when a short form is used for informed consent.

Short Form: The short form is a translated document summarizing the essential elements of informed consent in the subject’s preferred language.
Written Summary: This is a detailed document in English that outlines all aspects of the informed consent process.
Witness: An individual (over 18, fluent in both languages, not involved in the study) witnesses the researcher obtaining consent from the subject.
Signing: After the subject understands and agrees to participate, they sign the short form. The witness then signs both the short form and the written summary to confirm they witnessed the process and the subject’s agreement.
Therefore, it’s crucial for both the short form and the summary to be signed by the witness for proper documentation and ethical research practice.

Question 72

True/False
Form 1572 is the investigator statement

Answer 72

True
Form 1572, also known as the “Statement of Investigator,” is a document that must be completed by clinical investigators participating in research studies involving investigational new drugs, biologics, or medical devices in the United States. The purpose of this form is to provide the Food and Drug Administration (FDA) with essential information about the investigator’s qualifications, the study site, and the study itself. By signing Form 1572, investigators commit to conducting the study in accordance with the approved protocol, relevant regulations, and Good Clinical Practice (GCP) guidelines. This form plays a crucial role in ensuring the ethical conduct of clinical trials and the protection of human subjects.

Question 73

True/False
45 CFR Part 46 refers to the Code of Federal Regulations (CFR) that outlines the protection of human subjects in research activities conducted or supported by the U.S. Department of Health and Human Services (HHS).

Answer 73

True
Specifically, it is titled “Protection of Human Subjects.” These regulations are based on the ethical principles outlined in the Belmont Report and provide a framework for the conduct of research involving human subjects. The regulations cover various aspects of research, including the requirement for Institutional Review Board (IRB) review and approval, informed consent procedures, and the protection of vulnerable populations, such as children, pregnant women, and prisoners. Compliance with 45 CFR Part 46 is essential for institutions and researchers involved in HHS-funded or conducted research to ensure the ethical treatment and safety of human subjects.

Question 74

In a non-emergency situation, what conditions, if any, may subjects be enrolled into a study prior to IRB/IEC approval?

Answer 74

In a non-emergency situation, subjects cannot be enrolled into a study prior to IRB/IEC approval. This means that even if the investigator provides their written approval or if the study drug has an FDA approved marketing application, subjects still cannot be enrolled until the necessary IRB/IEC approval has been obtained. The FDA providing written approval of the IND also does not allow for subjects to be enrolled prior to IRB/IEC approval.

Question 75

The World Medical Association (WMA) ethical principles for medical research involving human subjects is called

Answer 75

The Declaration of Helsinki is a set of ethical principles for medical research involving human subjects, established by the World Medical Association (WMA). It provides guidelines for researchers to ensure the protection and well-being of human participants in research studies. The Belmont Report, the National Research Act, and the Nuremberg Code are also important documents related to research ethics, but they are not specifically associated with the WMA or medical research involving human subjects.

Question 76

The international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects is known as

Answer 76

Good Clinical Practices (GCP) is the international ethical and scientific quality standard for designing, conducting, recording, and reporting trials involving human subjects. GCP ensures that the rights, safety, and well-being of the participants are protected and that the data generated from the trials are reliable and credible. It provides guidelines on the ethical considerations, study design, participant recruitment, informed consent process, data collection and management, safety monitoring, and reporting of results. GCP is widely recognized and followed by regulatory authorities, research institutions, and pharmaceutical companies to ensure the highest standards of research integrity and participant protection.

Question 77

This form is used for the voluntary reporting of adverse events and product problems

Answer 77

The correct form is Form FDA 3500. Form FDA 3500, also known as the “Voluntary Adverse Event Report,” is used by healthcare professionals, consumers, and patients to voluntarily report adverse events and product problems related to drugs, biologics, medical devices, dietary supplements, and other FDA-regulated products. Reporting adverse events can help the FDA identify potential safety concerns, monitor product safety, and take appropriate actions to protect public health, such as issuing warnings or requiring label changes.

Question 78

Once the sponsor evaluates data from a clinical trial and decides the drug presents an immeasurable and significant risk to the subjects; the sponsor has [___] to discontinue the study.

Answer 78

5 working days
Although the specific regulations may vary by country and regulatory body, a common timeframe for a sponsor to report significant safety issues and make necessary changes to a clinical trial, including discontinuation, is within 5 working days (WD). In the event that a drug presents an immeasurable and significant risk to the subjects, the sponsor should work expeditiously to gather the necessary information and notify the appropriate parties, such as ethics committees and regulatory authorities, within this timeframe. The sponsor should also take prompt action to protect the safety and well-being of the subjects, which may include discontinuing the study or making significant modifications to the protocol.

Question 79

What is the minimum number of IRB members?

Answer 79

The minimum number of IRB members is 5 because having a minimum of 5 members ensures diversity and represents different perspectives and expertise. This allows for comprehensive review and evaluation of research proposals, ensuring ethical considerations are adequately addressed. With fewer than 5 members, there may not be enough diversity and expertise to effectively assess the ethical implications of the research.

Question 80

A subject has been enrolled on a study and was randomized to the non-treatment arm. The protocol outlines study procedures for all subjects to be performed within one week of enrollment. What study procedures should the subject follow?

Answer 80

This subject should undergo all study procedures as outlined in the protocol. Regardless of being randomized to the non-treatment arm, the protocol states that all subjects should undergo the study procedures within one week of enrollment. Therefore, this subject is still required to follow the protocol and complete all study procedures.

Question 81

True/False
A Short Form informed consent is a written summary of the ICF that is not to exceed one page.

Answer 81

False
Although a Short Form informed consent is indeed a written summary of the full informed consent form (ICF), it is not necessarily limited to one page. The purpose of a Short Form informed consent is to provide a simplified, easily understandable version of the full ICF, focusing on the key information that potential research subjects need to make an informed decision about participating in a study.
The Short Form typically includes a description of the study’s purpose, procedures, risks, and benefits, as well as the subject’s rights and responsibilities. It may also include contact information for the investigator or research team and a statement that the subject voluntarily agrees to participate.
The Short Form informed consent is often used in situations where the full ICF is too complex or lengthy for the target population, such as when working with individuals who may have difficulty understanding the full document due to language barriers, cognitive impairments, or other factors. The Short Form must be accompanied by an oral presentation of the complete informed consent information, and a witness should be present to attest that the oral presentation occurred and that the subject understood the information. Both the subject and the witness must sign the Short Form to document their agreement to participate in the research.

Question 82

An investigational drug can be exported from the U.S., if

Answer 82

Approval is granted after a written request is submitted to the FDAs International Affairs Staff Associate Commissioner.
This means that in order for an investigational drug to be exported from the U.S., a written request must be submitted to the FDAs International Affairs Staff Associate Commissioner and approval must be granted. This suggests that there is a regulatory process in place to ensure that the exportation of investigational drugs is done in a controlled and monitored manner.

Question 83

True/False
FDA may waive any of the requirements contained in the regulations, including the requirements for IRB review.

Answer 83

The FDA can waive regulations, including IRB review, if it’s in the public’s best interest or necessary to protect subjects’ rights and welfare. This might occur in emergencies where IRB review delays treatment for life-threatening conditions. The FDA considers various factors to ensure ethical principles are maintained and subjects’ rights are safeguarded. Waivers are granted cautiously to maintain the integrity of research and participant safety.

Question 84

Identify the manner in which the informed consent form (ICF) can be presented to the subject.

Answer 84

Reading the informed consent form (ICF) to the subject or their legally authorized representative (LAR) is a common practice, particularly in cases where the subject may have difficulty reading due to various reasons such as poor eyesight, illiteracy, or cognitive impairments. This method ensures that the subject or LAR fully understands the content and implications of the consent they are giving. It also allows for immediate clarification of any questions or concerns. This approach is in line with ethical standards which emphasize that the process of obtaining informed consent must ensure comprehension and voluntariness. Other methods listed, like mailing the ICF or leaving the subject to read it alone, may not adequately ensure understanding and are less personal, potentially compromising the integrity of the informed consent process.

Question 85

What is the primary responsibility of the Institutional Review Board (IRB) in clinical research?

Answer 85

The primary responsibility of the Institutional Review Board (IRB) is to protect the rights and welfare of participants involved in clinical research. The IRB reviews research protocols to ensure that the study is ethically conducted, that risks to participants are minimized, and that informed consent is properly obtained. The IRB’s role is crucial in maintaining the ethical integrity of the research process.

Question 86

When assessing drug risk assessment, what should be The Food and Drug Administration (FDA) focus?

Answer 86

When assessing drug risks, the FDA primarily focuses on whether the benefits of a drug outweigh its known and potential risks. This risk-benefit analysis is crucial for determining whether a drug should be approved for public use. The other factors, while important in different contexts, do not play a central role in the FDA’s risk assessment process.

Question 87

What form is used for the mandatory reporting of serious adverse events?

Answer 87

Form FDA 3500A is used for the mandatory reporting of serious adverse events, product problems, and medication errors associated with FDA-regulated products, such as drugs, biologics, and medical devices. This form is primarily intended for use by healthcare professionals, healthcare facilities, manufacturers, and importers to report serious events that occur during the use of these products. Reporting such events is essential to help the FDA monitor product safety, identify potential risks, and take appropriate actions to protect public health, including product label changes, safety warnings, or product recalls.

Question 88

True/False
A Clinical Hold is an order by FDA to the investigator to suspend or stop ongoing investigations.

Answer 88

False
A Clinical Hold is an order issued by the Food and Drug Administration (FDA) to the sponsor, not the investigator, to suspend or stop ongoing clinical investigations. This action is taken when the FDA has concerns about the safety of the study participants or the integrity of the study data. A Clinical Hold can be placed on a specific study or an entire clinical program for an investigational new drug (IND) or investigational device exemption (IDE). The sponsor must address the FDA’s concerns and provide adequate information to resolve the issues before the clinical hold can be lifted and the study resumed. Although investigators are not the direct recipients of the Clinical Hold order, they must comply with the suspension of the study and may need to collaborate with the sponsor to resolve the issues leading to the hold.

Question 89

True/False
An IND is always required before using an investigational new drug.

Answer 89

An IND isn’t always needed for investigational new drugs. Exceptions include using a marketed drug for an unapproved indication without a clinical investigation, specific Phase 1 studies with approved drugs, or emergencies when no alternative therapy exists. If the drug is used in a clinical investigation to gather data for FDA marketing approval or labeling changes, an IND application is required. This process ensures proper testing and monitoring, protecting participants’ safety and generating reliable data on the drug’s safety and efficacy.

Question 90

True/False
The IRB must determine that requirements for permission by parents or guardians and assent by children are met.

Answer 90

True
The IRB ensures that parental/guardian permission and child assent requirements are met in pediatric research, as per federal regulations. These requirements vary based on the research risk level and the child’s age, helping to protect children’s rights, safety, and well-being while considering their developmental and emotional needs.

Question 91

True/False
When using the short form informed consent, the witness and the person actually obtaining the consent from the subject shall each sign the short form in addition to the summary.

Answer 91

False
Study 21 CFR 50.27 (2) -The witness shall sign BOTH the short form and summary. Person actually obtaining consent shall sign ONLY a copy of the summary. (Subject ONLY has to sign the short form).

Question 92

True/False
Per 21 CFR Part 312, the sponsor must notify FDA and all participating investigators in an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting.

Answer 92

True
21 CFR 312.32(c)(1)

Question 93

The clinical investigator will update the financial disclosure information if any relevant changes occur during the investigation’s course and for _______ following the study’s completion.

Answer 93

The clinical investigator is required to update the financial disclosure information if any relevant changes occur during the investigation’s course and for 1 year following the study’s completion. This is important to ensure transparency and integrity in the research process and to identify any potential conflicts of interest that may arise. By updating the financial disclosure information for 1 year, it allows for a sufficient period of time to capture any changes that may occur after the study has ended.

Question 94

Significant risk device is defined as an investigational device that is:

Answer 94

A significant risk device is one that is intended as an implant and presents a potential for serious risk to the subject’s health, safety, or welfare, or is purported to be for a use in supporting or sustaining human life and presents a potential risk, or is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk.

Question 95

The 3 fundamental ethical principles for human subjects’ in research are:

Answer 95

The 3 fundamental ethical principles for human subjects in research are respect for persons, beneficence, and justice. These principles emphasize the importance of treating individuals with dignity and autonomy, ensuring their well-being and minimizing harm, and promoting fairness and equity in the distribution of research benefits and burdens. By adhering to these principles, researchers can ensure that their studies are conducted ethically and that the rights and welfare of the participants are protected.

Question 96

With respect to IRB/IEC membership, both the FDA and the ICH require that

Answer 96

Both the FDA and the ICH require that at least one member’s primary area of interest is in a nonscientific area. This means that there should be at least one member on the IRB/IEC whose expertise is not solely focused on scientific matters. This requirement ensures that the review board has a diverse range of perspectives and can consider the ethical, social, and cultural implications of the research being conducted. It helps to prevent any potential biases or conflicts of interest that may arise if all members have a purely scientific background.

Question 97

What is the purpose of the FDA form 3454?

Answer 97

Complete form 3454 if none of the investigators have any FDA required disclosures.
The applicant can submit a single completed Form FDA 3454 for all clinical investigators certifying to the absence of financial interests and append a list of those investigators to the form.

Question 98

What is the purpose of the FDA form 3455?

Answer 98

Complete form 3455 if any clinical investigator has a financial disclosure that is significant.
Applicants may submit a single FORM FDA 3455, with attachments clearly identifying all clinical investigators with information to disclose and, for each investigator, identifying the study, the specific details of their financial interests and arrangements and the steps taken to minimize the potential for bias.

Question 99

What are the Data Safety Monitoring Board (DSMB) responsibilities?

Answer 99

The primary responsibilities of the DSMB are to 1) periodically review and evaluate the accumulated study data for participant safety, study conduct and progress, and, when appropriate, efficacy, and 2) make recommendations to NIDCR concerning the continuation, modification, or termination of the trial.

Question 100

Informed consent documents must contain which of the following?
a. A description of the scientific background for conducting the investigation
b. An explanation of the purpose of the investigation
c. Contact information for the sponsor of the investigational drug/device
d. A description of the investigator’s responsibilities

Answer 100

b. An explanation of the purpose of the investigation

Question 101

Signed electronic records shall contain information associated with the signing that clearly indicates all of the following:

Answer 101

(1) The printed name of the signer;

(2) The date and time when the signature was executed; and

(3) The meaning (such as review, approval, responsibility, or authorship) associated with the signature.