ICH-E6 - Investigator, IRB/IEC and Sponsor

Question 1

The investigator should be able to demonstrate (e.g., based on retrospective data) a potential for recruiting the required number of suitable subjects within the agreed _______.

a. study duration
b. recruitment period
c. annual review period
d. site initiation

Answer 1

B. Recruitment Period

Question 2

The investigator should have sufficient _______ to properly conduct and complete the trial within the agreed trial period.

Answer 2

time

Question 3

The investigator should have available an adequate number of _______ and ________ for the foreseen duration of the trial to conduct the trial properly and safely.

Answer 3

qualified staff and adequate facilities

Question 4

During a trial who should be responsible for all trial-related medical (or dental) decisions?

Answer 4

A qualified physician (or dentist, when appropriate), who is an investigator or a sub-investigator for the trial

Question 5

True or False? During a subject’s participation in a trial, the investigator/institution should ensure that adequate medical care is provided to a subject for any adverse events, including clinically significant laboratory values, related to the trial. The investigator/institution should inform a subject when medical care is needed for intercurrent illness(es) of which the investigator becomes aware.

Answer 5

False, During and FOLLOWING participation

Question 6

True or False? It is recommended that the investigator inform the subject’s primary physician about the subject’s participation in the trial if the subject has a primary physician even if the subject doesn’t agree to the primary physician being informed.

Answer 6

False

Question 7

Does a trial investigator need to find out why a subject withdrew?

Answer 7

Yes, the investigator should make a reasonable effort to ascertain the reason(s), while fully respecting the subject’s rights

Question 8

Can the investigator start the trial before favorable IRB opinion?

Answer 8

Negative Ghost Rider

Question 9

What does the investigator need approved from the IRB to start the trial?

Answer 9

1. the trial protocol, 2. written informed consent form and consent form updates, 3. subject recruitment procedures (e.g., advertisements), 4.and any other written information to be provided to subjects.

Question 10

Does the IRB need the IB?

Answer 10

Yes, the investigator/institution should provide the IRB/IEC with a current copy of the Investigator’s Brochure. If the Investigator’s Brochure is updated during the trial, the investigator/institution should supply a copy of the updated Investigator’s Brochure to the IRB/IEC.

Question 11

Who should sign the protocol to confirm agreement that the trial will be followed in compliance of the protocol?

Answer 11

Investigator/Institution and sponsor

Question 12

When can the investigator implement deviation from and changes to the protocol?

Answer 12

where necessary to eliminate an immediate hazard(s) to trial subjects, or when the change(s) involves only logistical or administrative aspects of the trial (e.g., change in monitor(s), change of telephone number(s)).

Question 13

The Investigator can implement changes in the protocol and deviate from protocol as long as it gets approval from whom?

Answer 13

Sponsor and IRB/IEC

Question 14

If the investigator implements a deviation from, or a change of, the protocol to eliminate an immediate hazard(s) to trial subjects without prior IRB/IEC approval/favourable opinion. As soon as possible, the implemented deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be submitted to:

Answer 14

1. the IRB/IEC for review and approval 2. The sponsor for agreement 3. Regulatory Authorities (if required)

Question 15

Responsibility for investigational product(s) accountability at the trial site(s) rests with the _________.

Answer 15

investigator/institution.

Question 16

True or False? The sponsor should maintain records of the product’s delivery to the trial site, the inventory at the site, the use by each subject, and the return to the sponsor or alternative disposition of unused product(s).

Answer 16

False, The investigator/institution and/or a pharmacist or other appropriate individual, who is designated by the investigator/institution,

Question 17

True or False? The pharmacist should ensure that the investigational product(s) are used only in accordance with the approved protocol.

Answer 17

False - Investigator

Question 18

Can the investigator obtain IC before IRB approval?

Answer 18

No

Question 19

When obtaining IC and documenting it, what does the investigator comply to?

Answer 19

the applicable regulatory requirement(s), and should adhere to GCP and to the ethical principles that have their origin in the Declaration of Helsinki.

Question 20

True or False? None of the oral and written information concerning the trial, including the written informed consent form, should contain any language that causes the subject or the subject’s legally acceptable representative to waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution, the sponsor, or their agents from liability for negligence.

Answer 20

True

Question 21

What kind of language is used in the IC

Answer 21

non-technical

Question 22

Before informed consent may be obtained, the investigator, or a person designated by the investigator, should provide the subject or the subject’s legally acceptable representative _____to inquire about details of the trial and to decide whether or not to participate in the trial. A. Compensation B. Ample Time and Opportunity C. Ample Scientific Background D. All of the above

Answer 22

B. Ample time and Opportunity

Question 23

The informed consent needs to be signed by the subject or LAR?

Answer 23

False-Signed and dated.

Question 24

True or False? The IC needs to be signed by the site personnel obtaining consent?

Answer 24

False-Signed and dated

Question 25

If a subject is unable to read or if a legally acceptable representative is unable to read who should be present? A. The Investigator B. A Physician C. LAR D. Impartial Witness

Answer 25

D. Impartial Witness

Question 26

When does an impartial witness sign the IC?

Answer 26

After the written informed consent form and any other written information to be provided to subjects, is read and explained to the subject or the subject’s legally acceptable representative, and after the subject or the subject’s legally acceptable representative has orally consented to the subject’s participation in the trial and, if capable of doing so, has signed and personally dated the informed consent form, the witness should sign and personally date the consent form

Question 27

Both the informed consent discussion and the written informed consent form and any other written information to be provided to subjects should include explanations of the following: (Lots of them)

Answer 27

(a) That the trial involves research.
(b) The purpose of the trial.
(c) The trial treatment(s) and the probability for random assignment to each treatment.
(d) The trial procedures to be followed, including all invasive procedures.
(e) The subject’s responsibilities.
(f) Those aspects of the trial that are experimental.
(g) The reasonably foreseeable risks or inconveniences to the subject and, when applicable, to an embryo, fetus, or nursing infant.
(h) The reasonably expected benefits. When there is no intended clinical benefit to the subject, the subject should be made aware of this.
(i) The alternative procedure(s) or course(s) of treatment that may be available to the subject, and their important potential benefits and risks.

(j) The compensation and/or treatment available to the subject in the event of trial-related injury.
(k) The anticipated prorated payment, if any, to the subject for participating in the trial.
(l) The anticipated expenses, if any, to the subject for participating in the trial.
(m) That the subject’s participation in the trial is voluntary and that the subject may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled.
(n) That the monitor(s), the auditor(s), the IRB/IEC, and the regulatory authority(ies) will be granted direct access to the subject’s original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the subject, to the extent permitted by the applicable laws and regulations and that, by signing a written informed consent form, the subject or the subject’s legally acceptable representative is authorizing such access.

(o) That records identifying the subject will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. If the results of the trial are published, the subject’s identity will remain confidential.
(p) That the subject or the subject’s legally acceptable representative will be informed in a timely manner if information becomes available that may be relevant to the subject’s willingness to continue participation in the trial.

(q) The person(s) to contact for further information regarding the trial and the rights of trial subjects, and whom to contact in the event of trial-related injury.
(r) The foreseeable circumstances and/or reasons under which the subject’s participation in the trial may be terminated.
(s) The expected duration of the subject’s participation in the trial.
(t) The approximate number of subjects involved in the trial.

Question 28

Which of these is not included on the IC?

(a) That the trial involves research.
(b) The purpose of the trial.
(c) The trial treatment(s) and the probability for random assignment to each treatment.
(d) The trial procedures to be followed, including all invasive procedures.

(e) The other trial subjects

Answer 28

E.

Question 29

Prior to participation in the trial, the subject or the subject’s legally acceptable representative should receive a copy of:

A. The protocol

B. The Informed Consent

C. Signed and Date Informed Consent

D. Written Information Provided to Subjects

D. C and D.

E. All of the Above

Answer 29

D. C and D

Question 30

If a clinical trial includes subjects who can only be enrolled with consent of the subejcts LAR, you still have to obtain signature and date from the subject?

Answer 30

No-the subject should be informed about the trial to the extent compatible with the subject’s understanding and, if capable, the subject should sign and personally date the written informed consent.

Question 31

What is a non-therapeutic Trial?

Answer 31

non-therapeutic trial (i.e., a trial in which there is no anticipated direct clinical benefit to the subject),

Question 32

What conditions must be fullfiled for a non-therapeutic trial be conducted with consent from a LAR?

(a) The objectives of the trial can not be met by means of a trial in subjects who can give informed consent personally.
(b) The foreseeable risks to the subjects are low.
(c) The negative impact on the subject’s well-being is minimized and low.
(d) The trial is not prohibited by law.
(e) The approval/favourable opinion of the IRB/IEC is expressly sought on the inclusion of such subjects, and the written approval/ favourable opinion covers this aspect.

(f) all of the above

Answer 32

F. Such trials, unless an exception is justified, should be conducted in patients having a disease or condition for which the investigational product is intended

Question 33

Source Documents should be mainted in what style?

Answer 33

attributable, legible, contemporaneous, original, accurate, and complete.

Question 34

True or False?

Changes to source data should be traceable, should obscure the original entry, and should be explained if necessary (e.g., via an audit trail).

Answer 34

False, shouldn’t obsure original

Question 35

Any change in the CRF should be:

A. dated, initialed, and explained

B. dated, initialed, and explained and not obscure the original

C. Dated and initialed in the minimum

Answer 35

B. dated, initialed, and explained and not obscure the original​

Question 36

Essential Documents should be retained at the site for:

Answer 36

until at least 2-years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least 2-years have elapsed since the formal discontinuation of clinical development of the investigational product

Question 37

Whos responsibiltiy is it to inform the investigator/institution as to when documents no longer need to be retained?

Answer 37

It is the responsibility of the sponsor to inform the investigator/institution as to when these documents no longer need to be retained

Question 38

Upon request of the_____ the investigator/institution should make available for direct access all requested trial-related records. (Select all that apply)

A. monitor

B. auditor

C. Trial Subject

D. IRB/IEC, or regulatory authority,

Answer 38

All but C

Question 39

Who submites progress reports to the IRB/IEC annually or more frequently if requested?

A. Sponsor

B. Investigator

C. Monitor

Answer 39

B. The investigator should submit written summaries of the trial status to the IRB/IEC annually, or more frequently, if requested by the IRB/IEC.

Question 40

Who should promptly provide written reports to the sponsor, the IRB/IEC and, where applicable, the institution on any changes significantly affecting the conduct of the trial, and/or increasing the risk to subjects.

A. Trial Subjects

B. CRC

C. Investigator

Answer 40

The investigator should promptly provide written reports to the sponsor, the IRB/IEC (see 3.3.8) and, where applicable, the institution on any changes significantly affecting the conduct of the trial, and/or increasing the risk to subjects.

Question 41

What is immediately reported to the sponsor?

Answer 41

All SAE’s, except for those SAEs that the protocol or other document (e.g., Investigator’s Brochure) identifies as not needing immediate reporting. The immediate reports should be followed promptly by detailed, written reports.

The investigator should also comply with the applicable regulatory requirement(s) related to the reporting of unexpected serious adverse drug reactions to the regulatory authority(ies) and the IRB/IEC.

Question 42

True or False?

Adverse events and/or laboratory abnormalities identified in the protocol as critical to safety evaluations should be reported to the sponsor according to the reporting requirements and within the time periods specified by the sponsor in the protocol

Answer 42

True

Question 43

True or False

If the trial is prematurely terminated or suspended for any reason, the investigator/institution shouldn’t promptly inform the trial subjects, should assure appropriate therapy and follow-up for the subjects, and, where required by the applicable regulatory requirement(s), should inform the regulatory authority(ies).

Answer 43

False

Question 44

True or False?

If the investigator terminates or suspends a trial without prior agreement of the sponsor, the investigator should inform the institution where applicable, and the investigator/institution should promptly inform the sponsor and the IRB/IEC, and should provide the sponsor and the IRB/IEC a detailed written explanation of the termination or suspension.

Answer 44

True

Question 45

What should the investigator do if a sponsor terminates or suspends a trial?

Answer 45

the investigator should promptly inform the institution where applicable and the investigator/institution should promptly inform the IRB/IEC and provide the IRB/IEC a detailed written explanation of the termination or suspension.

Question 46

What does an investigator do if the IRB suspends approval of a trial?

Answer 46

the investigator should inform the institution where applicable and the investigator/institution should promptly notify the sponsor and provide the sponsor with a detailed written explanation of the termination or suspension.

Question 47

During the trial, who should implement a quality managment system?

Answer 47

The Sponsor

Question 48

True or False?

Sponsors should focus on trial activities essential to ensuring data entegrity and the reliability of trial results. Quality management includes the design of efficient clinical trial protocols and tools and procedures for data collection and processing, as well as the collection of information that is essential to decision making.

Answer 48

False-

Sponsors should focus on trial activities essential to ensuring Human Subject Protection and the reliability of trial results. Quality management includes the design of efficient clinical trial protocols and tools and procedures for data collection and processing, as well as the collection of information that is essential to decision making.

Question 49

The quality management system should use a ______ based approach?

Answer 49

The quality management system should use a risk-based approach as described below

Question 50

Define Risk Based Approaches to Quality Management Systems:

Answer 50

5.0.1 Critical Process and Data Identification
During protocol development, the sponsor should identify those processes and data that are critical to ensure human subject protection and the reliability of trial results.

5.0.2 Risk Identification
The sponsor should identify risks to critical trial processes and data. Risks should be considered at both the system level (e.g., standard operating procedures, computerized systems, personnel) and clinical trial level (e.g., trial design, data collection, informed consent process).

5.0.3 Risk Evaluation

The sponsor should evaluate the identified risks, against existing risk controls by considering:
(a) The likelihood of errors occurring.
(b) The extent to which such errors would be detectable.
(c) The impact of such errors on human subject protection and reliability of trial results.
5.0.4 Risk Control
The sponsor should decide which risks to reduce and/or which risks to accept. The approach used to reduce risk to an acceptable level should be proportionate to the significance of the risk. Risk reduction activities may be incorporated in protocol design and implementation, monitoring plans, agreements between parties defining roles and responsibilities, systematic safeguards to ensure adherence to standard operating procedures, and training in processes and procedures.
Predefined quality tolerance limits should be established, taking into consideration the medical and statistical characteristics of the variables as well as the statistical design of the trial, to identify systematic issues that can impact subject safety or reliability of trialresults. Detection of deviations from the predefined quality tolerance limits should trigger an evaluation to determine if action is needed.

5.0.5 Risk Communication
The sponsor should document quality management activities. The sponsor should communicate quality management activities to those who are involved in or affected by such activities, to facilitate risk review and continual improvement during clinical trial execution.
5.0.6 Risk Review
The sponsor should periodically review risk control measures to ascertain whether the implemented quality management activities remain effective and relevant, taking into account emerging knowledge and experience.
5.0.7 Risk Reporting
The sponsor should describe the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken in the clinical study report (ICH E3, Section 9.6 Data Quality Assurance).

Question 51

What is not a risk based approach to quality management systems?

A. Risk Review

B. Risk Reporting

C. Critical Process and Data Identification

D. Risk in unblinding

Answer 51

D.

Question 52

_______is responsible for implementing and maintaining quality assurance and quality control systems with written SOPs to ensure that trials are conducted and data are generated, documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory requirement(s).

Answer 52

The sponsor

Question 53

______________is responsible for securing agreement from all involved parties to ensure direct access (see 1.21) to all trial related sites, source data/documents , and reports for the purpose of monitoring and auditing by the sponsor, and inspection by domestic and foreign regulatory authorities.

Answer 53

The sponsor

Question 54

True or False?

Agreements, made by the sponsor with the investigator/institution and any other parties involved with the clinical trial, should be in writing in a separate agreement.

Answer 54

False,

Agreements, made by the sponsor with the investigator/institution and any other parties involved with the clinical trial, should be in writing, as part of the protocol or in a separate agreement.

Question 55

True or False?

A sponsor may transfer any or all of the sponsor’s trial-related duties and functions to a CRO, once done the ultimate responsibility for the quality and integrity of the trial data will reside with the CRO set forth in the contract

Answer 55

False-always resides with the sponsor.

Question 56

Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the ________.

Answer 56

Sponsor

Question 57

The ______ should designate appropriately qualified medical personnel who will be readily available to advise on trial related medical questions or problems. If necessary, outside consultant(s) may be appointed for this purpose

Answer 57

Sponsor

Question 58

What would a IDMC do?

Answer 58

(IDMC) to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial. The IDMC should have written operating procedures and maintain written records of all its meetings

Question 59

When using electronic trial data handling and/or remote electronic trial data systems, the sponsor should:

(a) Ensure and document that the electronic data processing system(s) conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistent intended performance (i.e., validation).

The sponsor should base their approach to validation of such systems on a risk assessment that takes into consideration the intended use of the system and the potential of the system to affect human subject protection and reliability of trial results.

(b) Maintains SOPs for using these systems.

The SOPs should cover system setup, installation, and use. The SOPs should describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. The responsibilities of the sponsor, investigator, and other parties with respect to the use of these computerized systems should be clear, and the users should be provided with training in their use.
(c) Ensure that the systems are designed to permit data changes in such a way that the data changes are documented and that there is no deletion of entered data (i.e., maintain an audit trail, data trail, edit trail).
(d) Maintain a security system that prevents unauthorized access to the data.
(e) Maintain a list of the individuals who are authorized to make data changes (see 4.1.5 and 4.9.3).
(f) Maintain adequate backup of the data.
(g) Safeguard the blinding, if any (e.g., maintain the blinding during data entry and processing).
ADDENDUM
(h) Ensure the integrity of the data including any data that describe the context, content, and structure. This is particularly important when making changes to the computerized systems, such as software upgrades or migration of data.

Answer 59

Just study this card

Question 60

If the sponsor discontinues the clinical development of an investigational product (i.e., for any or all indications, routes of administration, or dosage forms), the sponsor should maintain all sponsor-specific essential documents for at least _______ after formal discontinuation or in conformance with the applicable regulatory requirement(s).

A. 1 year

B. 2 Years

C. 3 Years

D. 5 Years

Answer 60

B. 2-years after formal discontinuation or in conformance with the applicable regulatory requirement(s).

Question 61

If the sponsor discontinues the clinical development of an investigational product, the sponsor should notify Whom?

Answer 61

all the trial investigators/institutions and all the regulatory authorities.

Question 62

The sponsor specific essential documents should be retained until at least ______ after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least _______ have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period however if required by the applicable regulatory requirement(s) or if needed by the sponsor.

A. 1 Year

B. 2 Years

C. 3 Years

D. 5 Years

Answer 62

B. for both

Question 63

The ______should inform the investigator(s)/institution(s) in writing of the need for record retention and should notify the investigator(s)/institution(s) in writing when the trial related records are no longer needed.

Answer 63

Sponsor

Question 64

Who is responsible for selecting the investigator and ensuring they have the qualified training, experience and time to complete the trial?

Answer 64

Sponsor

Question 65

Before entering an agreement with an investigator/institution to conduct a trial, the sponsor should provide the investigator(s)/institution(s) with the ______ and an up-to-date _______, and should provide sufficient time for the investigator/institution to review the protocol and the information provided

A. Protocol, Informed Consent

B. Investigators Brochure, Marketing Materials

C. Protocol, Investigators Brochure

D. Informed Consent, Investigators Brochure

Answer 65

C. Protocol, Investigators Brochure

Question 66

What agreements should the sponsor obtain from the investigator/institution in relation to doing a trial? And what should they sign?

Answer 66

(a) to conduct the trial in compliance with GCP, with the applicable regulatory requirement(s) (see 4.1.3), and with the protocol agreed to by the sponsor and given approval/favourable opinion by the IRB/IEC (see 4.5.1);
(b) to comply with procedures for data recording/reporting;
(c) to permit monitoring, auditing and inspection (see 4.1.4)
(d) to retain the trial related essential documents until the sponsor informs the investigator/institution these documents are no longer needed (see 4.9.4 and 5.5.12).

The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.

Question 67

Prior to initiating a trial, the ______should define, establish, and allocate all trial-related duties and functions.

Answer 67

sponsor

Question 68

If required by the applicable _________, the sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator/the institution against claims arising from the trial, except for claims that arise from malpractice and/or negligence

Answer 68

regulatory requirement(s)

Question 69

The financial aspects of the trial should be documented in an agreement between the _____and the _________.

Answer 69

sponsor, investigator/institution.

Question 70

What information about the IRB should the sponsor obtain from the Investigator/Institiution?

Answer 70

5. 11.1 The sponsor should obtain from the investigator/institution:
   (a) The name and address of the investigator’s/institution’s IRB/IEC.
   (b) A statement obtained from the IRB/IEC that it is organized and operates according to GCP and the applicable laws and regulations.
   (c) Documented IRB/IEC approval/favourable opinion and, if requested by the sponsor, a current copy of protocol, written informed consent form(s) and any other written information to be provided to subjects, subject recruiting procedures, and documents related to payments and compensation available to the subjects, and any other documents that the IRB/IEC may have requested.

Question 71

True or False?

When planning trials, the sponsor should ensure that sufficient safety and efficacy data from nonclinical studies and/or clinical trials are available to support human exposure by the route, at the dosages, for the duration, and in the trial population to be studied.

Answer 71

True

Question 72

The __________should ensure that the investigational product(s) (including active comparator(s) and placebo, if applicable) is characterized as appropriate to the stage of development of the product(s), is manufactured in accordance with any applicable GMP, and is coded and labelled in a manner that protects the blinding, if applicable. In addition, the labelling should comply with applicable regulatory requirement(s).

Answer 72

sponsor

Question 73

The _______should determine, for the investigational product(s), acceptable storage temperatures, storage conditions (e.g., protection from light), storage times, reconstitution fluids and procedures, and devices for product infusion, if any. The sponsor should inform all involved parties (e.g., monitors, investigators, pharmacists, storage managers) of these determinations.

Answer 73

sponsor

Question 74

T/F:

The IRB/IEC is responsible for supplying the investigator(s)/institution(s) with the investigational product(s).

Answer 74

False-Sponsor

Question 75

T/F:

The sponsor may supply an investigator/institution with the investigational product(s) until the sponsor obtains all required documentation (e.g., approval/favourable opinion from IRB/IEC and regulatory authority(ies)).

Answer 75

False-“should not supply”

Question 76

When the sponsor provides investigator written procedures for hadling and storage of IP what should it address? Pick one that doesn’t apply:

A. adequate and safe receipt

B. handling and storage,

C. dispensing

D. Dosage

E. retrieval of unused product from subjects,

F. return of unused investigational product(s) to the sponsor (or alternative disposition if authorized by the sponsor and in compliance with the applicable regulatory requirement(s)).

Answer 76

D Dosage

Question 77

True or False:

The sponsor should ensure that it is specified in the protocol or other written agreement that the investigator(s)/institution(s) provide direct access to source data/documents for trial-related monitoring, audits, IRB/IEC review, and regulatory inspection

Answer 77

True

Question 78

True or False?

The sponsor should verify that each subject has consented, in writing, to direct access to his/her original medical records for trial-related monitoring, audit, IRB/IEC review, and regulatory inspection

Answer 78

True

Question 79

Who is responsible for the ongoing safety evaluation of the investigational product(s)?

A. IRB/IEC

B. DSMB

C. Sponsor

D. All of the Above

Answer 79

C sponsor

Question 80

What does the sponsor have to expedite reporting of?

Answer 80

ADRs

Question 81

What is the purpose of trial monitoring?

Answer 81

(a) The rights and well-being of human subjects are protected.

(b) The reported trial data are accurate, complete, and verifiable from source documents.

(c) The conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with the applicable regulatory requirement(s).

Question 82

Who selects the montiors for a trial?

Answer 82

Sponsor

Question 83

True or False?

Statistically controlled sampling may be an acceptable method for selecting the data to be verified

Answer 83

True

Question 84

What sort of approach should a sponsor take to monitoring?

Answer 84

The sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The flexibility in the extent and nature of monitoring described in this section is intended to permit varied approaches that improve the effectiveness and efficiency of monitoring. The sponsor may choose on-site monitoring, a combination of on-site and centralized monitoring, or, where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan).

Question 85

What is centralized monitoring?

Answer 85

remote evaluation of accumulating data, performed in a timely manner, supported by appropriately qualified and trained persons (data managers, biostatisticans).

Question 86

a review of statistical analyses of data from centralized monitoring can be used to? (select all that apply)?

(a) identify missing data, inconsistent data, data outliers, unexpected lack of variability and protocol deviations.
(b) examine data trends such as the range, consistency, and variability of data within and across sites.
(c) evaluate for systematic or significant errors in data collection and reporting at a site or across sites; or potential data manipulation or data integrity problems.
(d) analyze site characteristics and performance metrics.
(e) select sites and/or processes for targeted on-site monitoring.

Answer 86

ALL

Question 87

5.18.4 Monitor’s Responsibilities
The monitor(s) in accordance with the sponsor’s requirements should ensure that the trial is conducted and documented properly by carrying out the following activities when relevant and necessary to the trial and the trial site:
(a) Acting as the main line of communication between the sponsor and the investigator.
(b) Verifying that the investigator has adequate qualifications and resources (see 4.1, 4.2, 5.6) and remain adequate throughout the trial period, that facilities, including laboratories, equipment, and staff, are adequate to safely and properly conduct the trial and remain adequate throughout the trial period.
(c) Verifying, for the investigational product(s):
(i) That storage times and conditions are acceptable, and that supplies are sufficient throughout the trial.
(ii) That the investigational product(s) are supplied only to subjects who are eligible to receive it and at the protocol specified dose(s).
(iii) That subjects are provided with necessary instruction on properly using, handling, storing, and returning the investigational product(s).
(iv) That the receipt, use, and return of the investigational product(s) at the trial sites are controlled and documented adequately.
(v) That the disposition of unused investigational product(s) at the trial sites complies with applicable regulatory requirement(s) and is in accordance with the sponsor.
(d) Verifying that the investigator follows the approved protocol and all approved amendment(s), if any.
(e) Verifying that written informed consent was obtained before each subject’s participation in the trial.
(f) Ensuring that the investigator receives the current Investigator’s Brochure, all documents, and all trial supplies needed to conduct the trial properly and to comply with the applicable regulatory requirement(s).

(g) Ensuring that the investigator and the investigator’s trial staff are adequately informed about the trial.
(h) Verifying that the investigator and the investigator’s trial staff are performing the specified trial functions, in accordance with the protocol and any other written agreement between the sponsor and the investigator/institution, and have not delegated these functions to unauthorized individuals.
(i) Verifying that the investigator is enroling only eligible subjects.
(j) Reporting the subject recruitment rate.
(k) Verifying that source documents and other trial records are accurate, complete, kept up-to-date and maintained.
(l) Verifying that the investigator provides all the required reports, notifications, applications, and submissions, and that these documents are accurate, complete, timely, legible, dated, and identify the trial.
(m) Checking the accuracy and completeness of the CRF entries, source documents and other trial-related records against each other. The monitor specifically should verify that:
(i) The data required by the protocol are reported accurately on the CRFs and are consistent with the source documents.
(ii) Any dose and/or therapy modifications are well documented for each of the trial subjects.
(iii) Adverse events, concomitant medications and intercurrent illnesses are reported in accordance with the protocol on the CRFs.
(iv) Visits that the subjects fail to make, tests that are not conducted, and examinations that are not performed are clearly reported as such on the CRFs.
(v) All withdrawals and dropouts of enrolled subjects from the trial are reported and explained on the CRFs.
(n) Informing the investigator of any CRF entry error, omission, or illegibility. The monitor should ensure that appropriate corrections, additions, or deletions are made, dated, explained (if necessary), and initialled by the investigator or by a member of the investigator’s trial staff who is authorized to initial CRF changes for the investigator. This authorization should be documented.
(o) Determining whether all adverse events (AEs) are appropriately reported within the time periods required by GCP, the protocol, the IRB/IEC, the sponsor, and the applicable regulatory requirement(s).
(p) Determining whether the investigator is maintaining the essential documents (see 8. Essential Documents for the Conduct of a Clinical Trial).
(q) Communicating deviations from the protocol, SOPs, GCP, and the applicable regulatory requirements to the investigator and taking appropriate action designed to prevent recurrence of the detected deviations.

Question 88

If or when sponsors perform audits, as part of implementing quality assurance, they should consider what?

Answer 88

Purpose-The purpose of a sponsor’s audit, which is independent of and separate from routine monitoring or quality control functions, should be to evaluate trial conduct and compliance with the protocol, SOPs, GCP, and the applicable regulatory requirements

Selection and Qualification of Auditors–should be independent and qualified and documented.

• *Auditing Procedures–(**a) The sponsor should ensure that the auditing of clinical trials/systems is conducted in accordance with the sponsor’s written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports.
  (b) The sponsor’s audit plan and procedures for a trial audit should be guided by the importance of the trial to submissions to regulatory authorities, the number of subjects in the trial, the type and complexity of the trial, the level of risks to the trial subjects, and any identified problem(s).
  (c) The observations and findings of the auditor(s) should be documented.
  (d) To preserve the independence and value of the audit function, the regulatory authority(ies) should not routinely request the audit reports. Regulatory authority(ies) may seek access to an audit report on a case by case basis when evidence of serious GCP non-compliance exists, or in the course of legal proceedings.
  (e) When required by applicable law or regulation, the sponsor should provide an audit certificate.

Question 89

Noncompliance with the protocol, SOPs, GCP, and/or applicable regulatory requirement(s) by an investigator/institution, or by member(s) of the sponsor’s staff should lead to prompt action by the _____to secure compliance

Answer 89

sponsor

Question 90

If noncompliance that significantly affects or has the potential to significantly affect human subject protection or reliability of trial results is discovered, the sponsor should __________________________?

Answer 90

the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions.

Question 91

If the monitoring and/or auditing identifies serious and/or persistent noncompliance on the part of an investigator/institution, the sponsor should DO WHAT?

Answer 91

terminate the investiga-tor’s/institution’s participation in the trial.

Question 92

When an investigator’s/institution’s participation is terminated because of noncompliance, the sponsor should DO WHAT?

Answer 92

notify promptly the regulatory authority(ies).

Question 93

If a trial is prematurely terminated or suspended, the sponsor should promptly inform ______, and the ________ of the termination or suspension and the reason(s) for the termination or suspension. The _____should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor or by the investigator/institution, as specified by the applicable regulatory requirement(s).

Answer 93

the investigators/institutions

regulatory authority(ies)

IRB/IEC

Question 94

If a trial is prematurely terminated does the sponsor still have to prepare Clinical Study reports and provide to regulatory authorities?

Answer 94

Yes

Question 95

For multicentre trials, the sponsor should ensure that:

A. All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor and, if required, by the regulatory authority(ies), and given approval/favourable opinion by the IRB/IEC.

B. The CRFs are designed to capture the required data at all multicentre trial sites. For those investigators who are collecting additional data, supplemental CRFs should also be provided that are designed to capture the additional data.

C. The responsibilities of coordinating investigator(s) and the other participating investigators are documented prior to the start of the trial.

D. All investigators are given instructions on following the protocol, on complying with a uniform set of standards for the assessment of clinical and laboratory findings, and on completing the CRFs.

E. Communication between investigators is facilitated.

F. All of the above

Answer 95

F