CPI Clinical Research & Study Design 2 — Questions and Answers
Question 1: In a crossover trial, what is the primary purpose of the washout period?
- To allow recruitment of additional participants
- To eliminate carryover effects from the first treatment (Correct answer)
- To assess long-term safety of the intervention
- To randomize participants to the second arm
Correct answer: To eliminate carryover effects from the first treatment
The washout period ensures the first treatment is cleared from participants before they receive the second, preventing carryover bias.
Question 2: Which study design is most appropriate for evaluating a rare adverse event that occurs in 1 in 10,000 patients?
- Randomized controlled trial
- Cohort study
- Case-control study (Correct answer)
- Cross-sectional survey
Correct answer: Case-control study
Case-control studies start with the outcome (rare event) and look backward, making them efficient for studying rare adverse events.
Question 3: What does the term 'intention-to-treat' (ITT) analysis mean?
- Only participants who completed the study are analyzed
- Participants are analyzed based on the treatment they actually received
- All randomized participants are analyzed in the group they were assigned to, regardless of adherence (Correct answer)
- Analysis is limited to participants who met all inclusion criteria
Correct answer: All randomized participants are analyzed in the group they were assigned to, regardless of adherence
ITT analysis preserves randomization integrity by including all participants in their assigned groups, even if they did not complete or adhere to the assigned treatment.
Question 4: A study reports an odds ratio of 0.5 for a drug compared to placebo. How should this be interpreted?
- The drug doubles the risk of the outcome
- The drug is associated with 50% lower odds of the outcome (Correct answer)
- The drug has no effect on the outcome
- The drug increases the odds of the outcome by 50%
Correct answer: The drug is associated with 50% lower odds of the outcome
An OR of 0.5 means the odds of the outcome in the drug group are half (50% lower) compared to the placebo group.
Question 5: Which allocation concealment method best prevents selection bias in an RCT?
- Sealed opaque envelopes prepared by the investigator
- Alternating assignment (every other patient)
- Centralized randomization via a telephone or web system (Correct answer)
- Assignment based on date of birth
Correct answer: Centralized randomization via a telephone or web system
Centralized randomization systems are inaccessible to enrolling investigators, providing the strongest protection against selection bias.
Question 6: In a clinical trial, a 'surrogate endpoint' is best described as:
- The primary clinical outcome of interest (e.g., mortality)
- A biomarker intended to predict a clinical outcome (Correct answer)
- An exploratory safety measure
- A patient-reported quality-of-life measure
Correct answer: A biomarker intended to predict a clinical outcome
Surrogate endpoints are biomarkers (e.g., HbA1c, tumor size) used as stand-ins for clinical outcomes, assumed to predict them.
Question 7: What is the main limitation of an open-label extension (OLE) study?
- It cannot collect long-term safety data
- Results are confounded because participants and investigators know the treatment (Correct answer)
- It requires a new IND submission
- Blinding is strengthened compared to the parent study
Correct answer: Results are confounded because participants and investigators know the treatment
In an OLE, unblinding introduces performance and detection bias, making it difficult to attribute outcomes solely to the drug.
CPI Clinical Research & Study Design 2
In a crossover trial, what is the primary purpose of the washout period?