Research and Development Flashcards

In a randomised controlled trial of a new sedation protocol in ICU patients, which statistical test is most appropriate for comparing time to extubation between two groups when the data is not normally distributed?

Answer: Mann-Whitney U test

The Mann-Whitney U test is a non-parametric test used to compare two independent groups when data is not normally distributed, making it appropriate for skewed time-to-event data.

A systematic review on vasopressor use in septic shock includes studies with significant clinical heterogeneity. Which approach best addresses this in a meta-analysis?

Answer: Use a random-effects model and report I² statistic

A random-effects model accounts for between-study variability, and the I² statistic quantifies the proportion of total variation attributable to heterogeneity.

A researcher wants to determine how many patients are needed to detect a 10% absolute reduction in 28-day mortality from 40% to 30% with 80% power and a 5% significance level. Which concept determines this calculation?

Answer: Effect size and variance

Sample size calculations require the expected effect size (absolute risk reduction) and variance (estimated from baseline event rate) along with desired power and alpha.

In an observational ICU study, patients who received early physiotherapy had lower 90-day mortality. However, these patients also had lower APACHE II scores. This is an example of which bias?

Answer: Confounding by indication

Confounding by indication occurs when the reason a treatment is given (or withheld) is itself associated with the outcome, distorting the apparent treatment effect.

Which pharmacokinetic parameter is most relevant when evaluating whether a drug achieves adequate concentrations at the site of infection in critically ill patients with augmented renal clearance?

Answer: Time above MIC (T>MIC)

For time-dependent antibiotics (e.g., beta-lactams), the percentage of time the free drug concentration exceeds the MIC is the primary pharmacodynamic target.

A clinical researcher wishes to measure ICU patients' quality of life six months after discharge. Which validated tool is most widely used for this purpose in critical care research?

Answer: EQ-5D-5L

The EQ-5D-5L is a generic, validated health-related quality of life instrument widely used as a patient-reported outcome measure in ICU survivorship research.

In adaptive clinical trial design, what is the primary advantage over a traditional fixed design?

Answer: It allows pre-specified modifications to the trial based on interim data

Adaptive designs allow pre-specified modifications such as sample size re-estimation or arm dropping based on interim analyses, increasing efficiency without inflating type I error.