2 - RCT Critical Appraisal 2** Flashcards
When are endpoints defined?
Before the trial starts
What is a primary endpoint?
Answers the most important question in the trial (ex: what is the average increase in survival?)
What is a secondary endpoint?
Has secondary objectives (ex: a drug designed to prevent diabetes-related deaths, might also have a measure of quality of life or microvascular outcomes)
Difference between soft and hard endpoints
- Soft endpoints = subjective measurements and observations (ex: pt reports feeling better or skin has fewer rashes)
- Hard endpoints = objective endpoints that are well-defined (ex: pounds lost at 6 months)
What is a surrogate endpoint?
- Used in place of a primary endpoint to speed up the approval process or prove that a drug is working
- Ex: new drug marketed to reduce death from diabetes, drug appears to reduce high blood sugar but will take several years to gather mortality data
- Often cheaper or easier to measure
- Weaker than hard indicators
What is a validated surrogate endpoint?
When clinical trials have shown that a certain surrogate endpoint is a reliable predictor of some health benefit
What are composite/ combined endpoints?
- Used when a study has a fairly rare primary endpoint
- Rare events may require a very large, expensive trial in order to get statistically significant results
- Ex: mortality is relatively rare, so a common composite endpoint might be hospitalizations and major adverse CV events
Advantages of RCTs
- Rigorous evaluation of single variable in a precisely defined pt population
- Limits bias by theoretically comparing 2 identical groups
- Results lend themselves to meta-analysis
Disadvantages of RCTs
- Expensive
- Time consuming
- Money source dictates research agenda
- Surrogate endpoints used to limit cost and time required for study
- Failure of randomization and/or blinding
- Unethical to randomize
What causes selection bias?
- Due to lack of concealment of allocation
- Due to attrition and differential losses
What causes information bias?
- Participant response bias (due to lack of blinding)
- Outcome ascertainment bis (due to lack of blinding)
What are the types of bias in RCTs?
- Selection bias
- Information bias
- Bias due to competing interests
- Reporting biases
What are the types of reporting biases?
- Publication bias
- Time lag bias
- Outcome reporting bias
Define selection bias
When there are systematic differences in the way participants are accepted or rejected for a trial, or in how the intervention is assigned to participants once they have been accepted
Define information bias
- When the results are systematically distorted by knowledge of which intervention each participant is receiving
- Can exaggerate the effect
How can ascertainment bias be minimized during randomization?
Blind the participant as to which intervention they are receiving
How can ascertainment bias be minimized during delivery of intervention?
Blind the individuals who administer the interventions
How can ascertainment bias be minimized during assessment of outcomes?
Blind the individuals who record the outcomes
How can ascertainment bias be minimized during data analysis/ manuscript?
Blind the statisticians
What is the intention to treat analysis?
All study participants are included in the analyses as part of the groups to which they were randomized regardless of whether they completed the study or not
What is the worst case scenario sensitivity analysis?
Assign the worst possible outcome to the missing px or time-points in the group that shows the best results and the best possible outcomes to the missing px or time-points in the group w/ the worst results
What is the opposite of the intention to treat analysis?
Per protocol analysis
What can happen when a study doesn’t use intention to treat analysis?
- Violates the principle of randomization, the remaining participants in the 2 groups can no longer be considered as balanced
- May make the tx look better than it actually is
