ICH E6(R2) 4.11.1: Investigators must “immediately report all serious adverse events to the sponsor except for those the protocol identifies as not requiring immediate reporting.”

IRB must also be informed promptly per 21 CFR 312.64(b) .

Follow-up information is submitted later as available.

Investigators are required to maintain accurate subject records, often referred to as case histories .

21 CFR 312.62(b): “An investigator shall prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation.”

ICH E6(R2) 4.9.0: Reinforces that investigators are responsible for recording, handling, and storing clinical trial data.

Incorrect options:

B: Investigators may present protocols but cannot vote on IRB approval.

C: Sponsor responsibility (ICH E6 §5.18).

D: Sponsors are responsible for IB updates (ICH E6 §7.3.1).

Correct answer: A.

An Independent Data Monitoring Committee (IDMC or DSMB) is a group of independent experts established to review accumulating safety and efficacy data during a trial. Their main role is to ensure subject protection and trial integrity.

ICH E6(R2) 5.5.1: “The sponsor may consider establishing an independent data-monitoring committee (IDMC) to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial.”

Thus, DSMBs/IDMCs do not perform trial approvals (A) , do not design trials (C) , and do not select investigators (D) . Their authority is strictly advisory, providing recommendations to sponsors about safety and whether continuation of the study is ethically justified. The sponsor makes the final decision, but DSMB recommendations are highly influential.

Therefore, the correct answer is B (Recommendations to stop a trial) .

ICH requires immediate reporting of all SAEs to the sponsor (except those protocol-identified as not requiring immediate reporting). Exact extract:

ICH E6(R2) 4.11.1: “The investigator should report all serious adverse events immediately to the sponsor except for those SAEs that the protocol… identifies as not needing immediate reporting.” Therefore, “Immediately” (A) is correct. The other timeframes are not aligned with ICH GCP for initial SAE notification from investigator to sponsor.

The investigator holds ultimate responsibility for all data reported.

ICH E6(R2) 4.9.1: “The investigator is responsible for the accuracy, completeness, legibility, and timeliness of the data reported to the sponsor on the CRFs and all required reports.”

Monitors (D) verify data accuracy but are not responsible for data quality. Quality specialists (B) and IRB staff (C) have no role in data entry.

Correct answer: A (The clinical investigator).

In device trials, unanticipated adverse device effects (UADEs) must be promptly reported.

21 CFR 812.150(a)(1): “An investigator shall submit to the sponsor and the reviewing IRB a report of any unanticipated adverse device effect as soon as possible, but in no event later than 10 working days after the investigator first learns of the effect .”

In this case, severe burns with blistering go beyond the anticipated effect of mild burns listed in the investigational plan. Therefore, it qualifies as a UADE and triggers expedited reporting. Options A, B, and C are too short; the regulation specifically mandates a 10 working day maximum timeframe.

Thus, the correct answer is D (10 working days) .

Source documents are the original records where trial data are first recorded, from which Case Report Form (CRF) entries are verified.

ICH E6(R2) 1.52: Defines source documents as “original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, pharmacy dispensing records, recorded data from automated instruments, etc.).”

ICH E6(R2) 8.3.13: Requires maintenance of “source documents” to verify data integrity and allow monitoring/audits.

Pharmacy dispensing records (D) fit this definition, as they show initial data on investigational product dispensing and accountability. In contrast, subject instruction sheets (A) are communication tools, SOPs (B) are procedural guides, and the protocol (C) is a governing document, none of which qualify as original data records.

Therefore, the correct answer is D (Pharmacy dispensing records) .

Phase IV studies (post-marketing) examine real-world safety and effectiveness.

ICH E8(R1): Describes Phase IV as “studies performed after drug approval to delineate additional information including the drug’s risks, benefits, and optimal use.”

They often test drugs in new or broader populations beyond original approval.

While dosing and schedules are Phase I–III, Phase IV focuses on new patient populations or long-term outcomes.

The FDA record retention requirement for investigational drug studies is clearly outlined in 21 CFR 312.57(c) and 21 CFR 312.62(c) .

21 CFR 312.57(c): “A sponsor shall retain the records and reports… for 2 years after a marketing application is approved for the drug; or, if an application is not approved, until 2 years after shipment and delivery of the drug for investigational use is discontinued and FDA has been so notified.”

21 CFR 312.62(c): Investigators also must retain study-related records for 2 years following the date a marketing application is approved or 2 years after the investigation is discontinued.

This requirement ensures FDA can audit investigational product data even after approval to confirm compliance and verify trial results. Longer retention (e.g., 15 years) may be institutional or sponsor policy but is not mandated by federal law.

Thus, the correct answer is A (2 years) .

When reviewing protocols, IRBs/IECs are primarily responsible for safeguarding human subjects by evaluating risks, benefits, and fairness in subject selection.

21 CFR 56.111(a)(3): “In making its determination the IRB shall determine that… selection of subjects is equitable.”

45 CFR 46.111(a)(3): Repeats this requirement, emphasizing fairness across gender, race, age, and socioeconomic status.

Other options:

Patient population availability (A) is a feasibility issue , addressed by investigators and sponsors, not IRBs.

Education of the study team (C) is confirmed by the sponsor and investigator , not IRB.

Funding sources (D) may raise conflict of interest concerns, but they are not IRB approval criteria per federal regulations.

Thus, IRBs focus on justice and fairness in subject selection as part of the Belmont Report principles.