The investigator is directly responsible for ensuring that the IRB/IEC reviews and approves the research both initially and on a continuing basis. This responsibility is not delegable to the sponsor or study staff.

ICH E6(R2) 4.4.1: “Before initiating a trial, the investigator/institution should have written and dated approval/favorable opinion from the IRB/IEC for the trial protocol, written informed consent form, consent form updates, and any other written information to be provided to subjects.”

21 CFR 312.66: “An investigator shall assure that an IRB that complies with the requirements… will be responsible for the initial and continuing review and approval of the proposed clinical study.”

This means that while the sponsor submits documents to the FDA and oversees general compliance, the investigator has the obligation to obtain and maintain IRB approval at their site. The monitor or study coordinator may assist in documentation, but legal responsibility rests with the investigator.

Thus, the correct answer is C (The investigator) .

Providing a copy of the signed consent form to subjects is a mandatory requirement.

21 CFR 50.27(a): “A copy shall be given to the person signing the form.”

ICH E6(R2) 4.8.11: Reinforces that “a copy of the signed and dated written informed consent form should be given to the subject.”

Failure to provide this copy constitutes a direct violation of informed consent regulations.

Other issues:

A & C concern proper short form process but do not invalidate informed consent if a copy was provided.

D concerns sponsor template, but the site’s responsibility is ensuring use of IRB-approved version.

Correct answer: B.

Monitoring ensures trial integrity and subject safety.

ICH E6(R2) 5.18.3: “The sponsor should ensure that the trials are adequately monitored. The determination of the extent and nature of monitoring should be based on considerations such as the objective, purpose, design, complexity, blinding, size, and endpoints of the trial.”

Monitoring must occur before (initiation visit), during (periodic), and after (closeout).

It is not limited to fixed weekly or monthly intervals (A, B) and not as infrequent as yearly (D). Instead, it is risk-adapted and flexible , but must cover all phases of the study.

Correct answer: C (Timely manner before, during, and after).

21 CFR 312.32(c)(1)(ii): Sponsors must notify all participating investigators of any serious and unexpected suspected adverse reactions.

Investigators then inform IRBs and subjects as appropriate.

Investigators must document the receipt, use, return, or alternative disposition of investigational product (IP).

ICH E6(R2) 4.6.3: Requires investigators to maintain records of IP delivery, inventory, use by subjects, and return/disposition.

ICH E6(R2) 8.2.14–8.2.16: Essential documents include shipment records, accountability logs, and inventory records.

However, certificates of destruction are generated and retained by the sponsor (or authorized destruction facility), not required at the site unless the destruction occurred there. In this scenario, all IP was returned to the sponsor, so no destruction certificate would exist at the site.

Thus, the correct answer is D (Certificate of destruction).

Record retention requirements ensure regulatory access to data even after development is discontinued.

21 CFR 312.62(c): “An investigator shall retain records… for 2 years after the date a marketing application is withdrawn or discontinued and FDA is notified.”

In this case, development was terminated 15 May 2019 . Therefore, the 2-year clock starts at discontinuation. Two years later is 15 May 2021 , but FDA requires records to be maintained until after the 2-year period ends. The earliest permissible destruction date is 16 May 2022 (C).

Options A and B are premature; D (2034) is far beyond requirements.

Thus, the correct answer is C (16 May 2022).

The informed consent document (ICD) is a cornerstone of ethical clinical research, ensuring voluntary participation and protection of subject rights.

21 CFR 50.25(a): Requires the consent form to contain all basic elements , including study purpose, risks, benefits, alternatives, confidentiality, compensation, and voluntariness.

ICH E6(R2) 4.8.10: Expands on these requirements, ensuring the ICD contains every mandated element without omission.

Thus, the correct statement is that the ICD must include all applicable mandated basic elements (D). Options A and B confuse who signs—subjects or legally authorized representatives sign when applicable, not the IRB chair. Option C is incorrect because leaving out elements would violate compliance.

Correct answer: D.

This question tests drug accountability and dosing calculation, which is central to ICH E6(R2) 4.6 (Investigational product management). Subjects must receive the correct supply and any discrepancy must be reconciled.

The prescribed regimen is 2 mg twice daily = 4 mg per day. With 1 mg tablets, this equals 4 tablets daily. Over 10 days, the subject should consume 40 tablets (4 × 10 = 40). Since 45 tablets were dispensed, the subject should have 5 tablets remaining after 10 days.

Accurate accountability ensures trial integrity and subject safety. Investigators are responsible for maintaining investigational product (IP) records, including dispensing, usage, and returns. According to ICH:

4.6.3: “The investigator/institution should maintain records of the product’s delivery to the trial site, the inventory, the use by each subject, and the return to the sponsor or alternative disposition.”

4.6.5: “The investigator should ensure that investigational products are used only in accordance with the approved protocol.”

Thus, the correct answer is C (5 tablets remain). This reflects proper dosing compliance and highlights the importance of meticulous IP tracking in clinical trials.

Serious adverse events are subject to expedited reporting requirements.

ICH E2A 3.2.2: “Fatal or life-threatening unexpected ADRs should be reported as soon as possible but no later than 7 calendar days after first knowledge.”

ICH E2A 3.2.3: Other serious unexpected events must be reported within 15 days.

Thus, the 7-day rule applies to life-threatening and unexpected events (as in this case).

Correct answer: B (7 days).

Minimal risk determination is a regulatory function of the IRB/IEC.

45 CFR 46.102(j): Defines minimal risk as harm or discomfort not greater than those ordinarily encountered in daily life.

45 CFR 46.109(a): The IRB has authority to approve, require modifications, or disapprove research, including assessment of risk level .

Investigators may propose a study as minimal risk, but only the IRB/IEC can formally classify it .

This ensures independent, unbiased evaluation of risk, protecting participants from investigator or sponsor bias.