CCRP Certified Clinical Research Professional (CCRP) Questions and Answers

The investigator has ultimate responsibility for site staff qualifications.

ICH E6(R2) 4.2.4:“The investigator should ensure that all persons assisting with the trial are adequately informed about the protocol, the investigational product, and their trial-related duties and functions.”

ICH E6(R2) 4.1.5:Investigator must maintain current documentation of staff qualifications.

While sponsors and monitors oversee compliance, accountability rests with theclinical investigator. Coordinators may implement duties, but do not hold legal responsibility.

Correct answer:B (The clinical investigator).

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 than7 calendar daysafter first knowledge.”

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

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

Correct answer:B (7 days).

21 CFR 11.100(a):Requires that electronic signatures be “unique to one individual and shall not be reused or reassigned to anyone else.”

This ensures accountability and audit trail integrity.

ICH E6(R2) 4.2.4:“The investigator should ensure that all persons assisting with the trial are adequately informed about the protocol, investigational product, and trial-related duties.”This responsibility cannot be delegated to sponsor or IRB.

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 ofrisk level.

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

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

Upon study closure, investigators must maintain documentation that allows subject data to be linked back if necessary. TheSubject Identification Code Listis a key essential document for ensuring traceability while maintaining confidentiality.

ICH E6(R2) 8.3.21:“Subject Identification Code List — A list of all subjects randomized to trial numbers, allowing investigator to identify each subject in case follow-up is required. This list should be kept in a confidential manner and retained for the maximum retention period.”

ICH E6(R2) 8.4:Essential documents for investigators include items needed for subject identification, protocol compliance, and trial closure.

Other listed documents (randomization list, monitoring report, audit certificate) are maintained by the sponsor, not the investigator. Thesubject code listensures that in the event of a safety issue, regulatory authority queries, or subject withdrawal, the investigator can trace back records.

Thus, the correct answer isB (Completed Subject Identification Code List).

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 per21 CFR 312.64(b).

Follow-up information is submitted later as available.

ICH E6(R2) 5.2.1:“The sponsor is responsible for implementing and maintaining quality assurance and quality control systems… including allocation of trial-related duties.”

Although tasks may be delegated to CROs or site staff, accountability remains with thesponsor.

IRBs/IECs must retain records to permit evaluation of compliance.

ICH E6(R2) 3.4.2:“IRB/IEC should retain all relevant records (e.g., written procedures, membership lists, lists of occupations/affiliations of members, submitted documents, minutes of meetings, and correspondence) for at least3 years after completion of the trial.”

Extended retention (B–D) may occur institutionally, but ICH minimum is3 years.

Correct answer:A (At least 3 years).

ICH E6(R2) 5.5.12 & 8.1:Essential documents must be retained2 years after the last approval of a marketing application in an ICH region and until no applications are pending, or2 years after discontinuation of development.

This ensures availability for inspection.

Quality assurance (QA)is proactive and systematic, designed to prevent errors and ensure compliance.

ICH E6(R2) 1.46:Defines QA as “all those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented, and reported in compliance with GCP and applicable regulatory requirements.”

Option A describes IRB responsibilities, Option C describesaudit, and Option D describes protocol approval processes. OnlyBaccurately matches the ICH definition of QA. QA is distinct fromquality control (QC), which is operational and focused on detection of issues during conduct.

Thus, the correct answer isB.

Theshort form consent processis permitted when the subject is presented with a brief written statement that they were informed of the study, supplemented by an oral presentation.

21 CFR 50.27(b)(2):Requires the short form to be signed by the subject (or legally authorized representative)and a witness.

The witness ensures that oral consent was properly conveyed and understood.

The person obtaining consent must sign aseparate written summary, but not the short form itself.

Thus, the accurate answer isA: subject (or LAR) + witness.

When a physician investigates amedical device for a new use (off-label indication), FDA regulations classify this as aSignificant Risk Device Study, requiring anInvestigational Device Exemption (IDE)in addition to IRB approval.

21 CFR 812.20(a):“A sponsor shall submit an application to FDA for aninvestigational device exemption (IDE)if the device is to be used in a clinical investigation to determine safety and effectiveness.”

21 CFR 812.2(b):Significant Risk device studies requireboth FDA and IRB approvalbefore initiation.

An IND (B) applies to drugs and biologics, not devices. Manufacturer permission (A, D) is not a regulatory requirement, although collaboration may be necessary. OHRP approval is not applicable.

Thus, the correct answer isC (IRB/IEC approval and an FDA IDE).

The regulatory binder (investigator site file) must contain documents verifying qualifications of all personnel. These include curricula vitae (CVs), professional licenses, and training certificates.

ICH E6(R2) 4.1.5: “The investigator should ensure that all persons assisting with the trial are qualified by education, training, and experience… Current curriculum vitae and/or other relevant documents evidencing qualifications should be maintained.”

21 CFR 312.53(c)(1): Sponsors must select investigators qualified “by training and experience,” and investigators must provide sufficient documentation, typically updated CVs.

Letters of promotion (A), training brochures (B), or performance reviews (C) may remain in personnel files but are not required regulatory documents. The only acceptable regulatory proof is an updated CV (D), which reflects the individual’s training and qualifications for their new role.

Therefore, the correct answer is D (Updated CV). This ensures compliance with ICH and FDA requirements for staff qualification documentation in clinical research.

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 anyunanticipated adverse device effectas soon as possible, but in no event later than10 working days after the investigator first learns of the effect.”

In this case,severe burns with blisteringgo beyond the anticipated effect of mild burns listed in the investigational plan. Therefore, it qualifies as aUADEand triggers expedited reporting. Options A, B, and C are too short; the regulation specifically mandates a10 working day maximumtimeframe.

Thus, the correct answer isD (10 working days).

Recruitment materials must be reviewed to protect subjects from misleading or coercive messaging.

21 CFR 56.111(a)(3):IRBs must ensure equitable subject selection.

ICH E6(R2) 3.1.2:IRBs safeguard rights, safety, and well-being, including review of recruitment strategies.

FDA and OHRP do not approve recruitment materials; responsibility lies withIRB/IEC.

ICH E6(R2) 4.6.1:“Responsibility for investigational product accountability at the trial site rests with the investigator.”

May delegate to pharmacist or coordinator, butultimate responsibilitylies with investigator.

21 CFR 312.32(c)(2):Life-threatening or fatal unexpected adverse events must be reported within7 calendar days.Other serious unexpected events are reported within 15 days.

21 CFR 56.110(b):IRBs may use expedited review forminor changesin previously approved research.

Expedited review cannot be used for initial reviews of high-risk protocols or major modifications.

Correct answer isD.

For IRB/IEC submissions, investigators must disclose subject-related information that may impact voluntariness or fairness of participation.

21 CFR 56.111(a)(3):The IRB must ensure that subject selection is equitable.

21 CFR 50.25(a)(3):Requires disclosure of “any compensation and/or medical treatments available if injury occurs.”

ICH E6(R2) 4.8.10(n):Informed consent should describe “any compensation and/or reimbursement to subjects.”

Thus,compensation amountsmust be reviewed by IRB/IEC to ensure they are not coercive or excessive. Budgets (A), marketing plans (C), and contracts (D) are administrative and not part of IRB submission requirements.

Correct answer:B (The amount of payments and compensation to subjects).

ICH E6(R2) 4.6.1:The investigator is responsible for investigational product accountability at the site.

21 CFR 312.61:Investigators must administer the investigational drug only to subjects under their supervision.

The IRB maintains meeting minutes (A), preclinical studies are sponsor tasks (B), and financial interest documentation (C) is covered under sponsor reporting. Thus,D is correct.

Audits are part of sponsor quality assurance to ensure trial compliance.

ICH E6(R2) 5.19.3:“The sponsor’s auditing procedures should include the provision of anaudit certificatewhere required.”

ICH E6(R2) 8.2.20:Audit certificates are essential documents generated and retained by the sponsor.

IRBs (A), regulators (B), and DSMBs (C) are not responsible for audit documentation. Therefore, only thesponsorissues and maintains audit certificates, providing them to sites when appropriate.

Correct answer:D.

TheBelmont Report (1979)establishedthree key ethical principles:

Respect for Persons:Requires informed consent, recognition of autonomy, and protection of vulnerable individuals.

Beneficence:Obligation to maximize benefits and minimize harm.

Justice:Ensuring fairness in subject selection and distribution of research burdens/benefits.

Voluntary informed consent embodiesRespect for Persons, as subjects are given adequate information and freedom of choice. “Do no harm” (A) is a Hippocratic principle but not Belmont terminology.

Thus, the correct answer isB (Respect for persons).

ICH E6(R2) 4.8.10(n):Consent must include explanation about confidentiality and possible publication.

If not included, specificsubject consentmust be obtained before publishing identifiable results.

Thus, subject’s explicit permission is required.

21 CFR 11.10:Requires validation, audit trails, secure access, but does not mandate printing capability.Thus, (D) is the exception.

TheInvestigator’s Brochure (IB)compilesclinical and nonclinical dataon an investigational product relevant to human study.

ICH E6(R2) 7.2.3:The IB should summarizenonclinical pharmacology, toxicology, pharmacokinetics, and efficacy data, including results of animal studies.

ICH E6(R2) 7.2.4:It should also includeavailable clinical trial dataand safety experience.

The “results of recent nude mouse study” (B) are nonclinical data, which appropriately belong in the IB. Lab draw requirements (A), dispensing instructions (C), and schedules of events (D) are operational/procedural and are found in theprotocol, not the IB.

Thus, the correct answer isB (Results of recent nude mouse study).

ICH E6(R2) 5.6.1:“The sponsor should ensure agreement from the investigator/institution on the financial aspects of the trial.”This ensures transparency in compensation, reimbursement, and budget.

Sponsors must reportserious, unexpected, and suspected adverse reactions (SUSARs)to the FDA.

21 CFR 312.32(c)(2):“Any adverse experience associated with the use of the drug that is bothserious and unexpectedshall be reported…as soon as possible but no later than 7 calendar daysafter the sponsor’s initial receipt of the information, if it is fatal or life-threatening.”

ICH E2A 4.2:Requires expedited reporting oflife-threatening or fatal SUSARswithin 7 days.

Among the options, only (C) —death from arrhythmias not previously identified in the Investigator’s Brochure and suspected to be drug-related— meets the definition of a SUSAR requiring7-day expedited reporting. Events already listed in the IB (A, D) or unrelated to the drug (B) do not trigger expedited reporting.

Thus, the correct answer isC.

Informed consent is a fundamental ethical requirement. If it is violated in a device trial, the FDA requires rapid reporting.

21 CFR 812.150(b)(5):States that a sponsor shall submit to FDA “any report of use of a device without obtaining informed consent, within5 working daysafter the sponsor first receives notice of such use.”

This expedited reporting ensures FDA oversight of serious violations and protection of human subjects.

Incorrect options:

A (1 day) is overly strict and not codified.

C (10 days) and D (30 days) are too delayed to meet regulatory intent of immediate oversight.

Thus, the correct timeline iswithin 5 working days.

The IRB/IEC is empowered to protect subjects and ensure informed consent remains accurate, complete, and understandable.

ICH E6(R2) 3.1.2:“The IRB/IEC should safeguard the rights, safety, and well-being of all trial subjects. Special attention should be paid… when considering the adequacy and completeness of the written information to be provided to the subjects.”

21 CFR 56.109(b):“The IRB shall require that information given to subjects as part of informed consent is in accordance with §50.25.The IRB may require that information, in addition to that specifically mentioned in §50.25, be given to the subjects when in its judgment the information would meaningfully add to the protection of the rights and welfare of subjects.”

This confirms that the IRB/IEC has unilateral authority to request additional information at any time, regardless of sponsor or investigator agreement.

Thus, the correct answer isA (At any time, at the discretion of the IRB/IEC).

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).

TheBelmont Report (1979), issued by the U.S. National Commission, identifiesthree core ethical principlesguiding human subject research:

Respect for Persons(informed consent, autonomy, protection of vulnerable populations).

Beneficence(maximize benefits, minimize harms).

Justice(fairness in subject selection and treatment).

TheNuremberg Code (1947)was developed post-WWII to prevent unethical experiments.

TheDeclaration of Helsinki (1964, updated)is a World Medical Association document guiding international physician research ethics.

TheICH Guidelines (1996)outline harmonized regulatory requirements for good clinical practice.

Only the Belmont Report fits the description of a U.S.-based, principle-driven framework for human research ethics.

Thus, the correct answer isD (The Belmont Report).

21 CFR 312.23(a):Requires cover sheet, CMC information, and IB.

Financial disclosureis required separately under21 CFR 54, not part of IND content.

Belmont Report:“Respect for Persons” incorporates two ethical convictions: treating individuals as autonomous agents and protecting those with diminished autonomy (e.g., prisoners).

Prisoners require special safeguards because of restricted liberty and potential coercion.

Endpoint data collection is based onprotocol designand subject compliance, not CRF formatting.

ICH E6(R2) 4.9.0:Investigator responsible for data accuracy regardless of CRF complexity.

Theprotocolgoverns all trial conduct, including whether subjects should be replaced when they withdraw.

ICH E6(R2) 6.0:The protocol must contain “detailed information on trial design, methodology, statistical considerations, and the organization of the trial.”

ICH E6(R2) 6.9.2:The section on “Subject withdrawal or discontinuation” specifies “whether and under what conditions subjects may be replaced.”

Other documents serve different functions: the DSM plan (A) manages safety oversight, the IB (C) summarizes product background, and the consent form (D) explains subject rights but does not guide study conduct. Only theprotocolprovides the operational answer regarding replacement.

Thus, the correct answer isB (The protocol).