CCRA Certified Clinical Research Study 5 — Questions and Answers
Question 1: A sponsor conducts a centralized statistical monitoring (CSM) review and identifies Site B as having an unusually low rate of adverse event reporting compared to similar sites. What is the most appropriate interpretation?
- Site B has the best-performing subjects in the trial
- Site B may have an underreporting issue that warrants targeted on-site investigation (Correct answer)
- CSM results are unreliable and should be disregarded
- The site should be closed immediately without further review
Correct answer: Site B may have an underreporting issue that warrants targeted on-site investigation
Anomalously low AE rates detected by CSM are a red flag for underreporting, which requires a targeted monitoring visit to assess data integrity and site practices.
Question 2: Which phase of clinical development is primarily designed to establish the maximum tolerated dose (MTD) and evaluate pharmacokinetics of an investigational drug?
- Phase II
- Phase I (Correct answer)
- Phase III
- Phase IV
Correct answer: Phase I
Phase I trials are first-in-human studies focused on safety, tolerability, pharmacokinetics, and dose escalation to find the MTD in a small cohort.
Question 3: Under FDA regulations, what is required when a sponsor makes a 'major' change to an approved IND protocol?
- No notification is required for protocol changes
- A protocol amendment must be submitted to the FDA before implementing the change (Correct answer)
- The sponsor can implement the change after notifying the FDA within 30 days
- Only IRB approval is needed, not FDA notification
Correct answer: A protocol amendment must be submitted to the FDA before implementing the change
Major protocol amendments under an IND must be submitted to FDA prior to implementation, as they may affect subject safety or study integrity.
Question 4: A CRA is conducting a pre-study site selection visit. Which factor would be the STRONGEST disqualifier for site selection?
- The site has no prior experience with this specific indication
- The PI is currently under FDA investigation for GCP non-compliance (Correct answer)
- The site's patient population is slightly smaller than ideal
- The site uses paper CRFs rather than an EDC system
Correct answer: The PI is currently under FDA investigation for GCP non-compliance
An active FDA investigation for GCP non-compliance creates significant regulatory and data integrity risks that would typically disqualify a site from participation.
Question 5: What does 'SUSAR' stand for and what is its significance in clinical trial safety reporting?
- Suspected Unexpected Serious Adverse Reaction — an SAE that is both unexpected and causally related to the investigational product (Correct answer)
- Standard Unblinded Safety Adverse Report — a routine safety data submission
- Systemic Unexpected Study Adverse Result — a statistical outlier in safety data
- Subject Unanticipated Serious Adverse Response — any unexpected hospital admission
Correct answer: Suspected Unexpected Serious Adverse Reaction — an SAE that is both unexpected and causally related to the investigational product
A SUSAR is a Suspected Unexpected Serious Adverse Reaction — an SAE with a reasonable causal relationship to the IP that is not consistent with the IB; these have expedited reporting requirements.
Question 6: According to ICH E6(R2), sponsors must ensure that clinical trials are conducted in accordance with the protocol and GCP. Which mechanism is primarily used to fulfill this oversight obligation?
- Annual IRB review of all site data
- A monitoring program proportionate to the risk and complexity of the trial (Correct answer)
- Mandatory weekly phone calls between CRAs and investigators
- Submission of all raw data to FDA for independent review
Correct answer: A monitoring program proportionate to the risk and complexity of the trial
ICH E6(R2) requires sponsors to implement risk-based monitoring programs, scaling oversight intensity to the trial's risk profile and complexity.
Question 7: A subject withdraws consent during a clinical trial. Which of the following best reflects the investigator's obligations regarding that subject's already-collected data?
- All data collected must be destroyed immediately upon withdrawal
- Previously collected data may generally be retained and used per the informed consent signed at enrollment (Correct answer)
- The subject's data must be excluded from all analyses regardless of consent language
- The sponsor must seek new consent from the subject to retain any data
Correct answer: Previously collected data may generally be retained and used per the informed consent signed at enrollment
Data collected prior to withdrawal may typically be retained and used as described in the original ICF; subjects can withdraw from further participation but cannot generally require retroactive data deletion in regulated trials.
CCRA Certified Clinical Research Study 5
A sponsor conducts a centralized statistical monitoring (CSM) review and identifies Site B as having an unusually low rate of adverse event reporting compared to similar sites.
What is the most appropriate interpretation?