2 - RCT Critical Appraisal 2**

Question 1

When are endpoints defined?

Answer 1

Before the trial starts

Question 2

What is a primary endpoint?

Answer 2

Answers the most important question in the trial (ex: what is the average increase in survival?)

Question 3

What is a secondary endpoint?

Answer 3

Has secondary objectives (ex: a drug designed to prevent diabetes-related deaths, might also have a measure of quality of life or microvascular outcomes)

Question 4

Difference between soft and hard endpoints

Answer 4

• 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)

Question 5

What is a surrogate endpoint?

Answer 5

• 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

Question 6

What is a validated surrogate endpoint?

Answer 6

When clinical trials have shown that a certain surrogate endpoint is a reliable predictor of some health benefit

Question 7

What are composite/ combined endpoints?

Answer 7

• 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

Question 8

Advantages of RCTs

Answer 8

• 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

Question 9

Disadvantages of RCTs

Answer 9

• 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

Question 10

What causes selection bias?

Answer 10

• Due to lack of concealment of allocation

- Due to attrition and differential losses

Question 11

What causes information bias?

Answer 11

• Participant response bias (due to lack of blinding)

- Outcome ascertainment bis (due to lack of blinding)

Question 12

What are the types of bias in RCTs?

Answer 12

• Selection bias
• Information bias
• Bias due to competing interests
• Reporting biases

Question 13

What are the types of reporting biases?

Answer 13

• Publication bias
• Time lag bias
• Outcome reporting bias

Question 14

Define selection bias

Answer 14

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

Question 15

Define information bias

Answer 15

• When the results are systematically distorted by knowledge of which intervention each participant is receiving
• Can exaggerate the effect

Question 16

How can ascertainment bias be minimized during randomization?

Answer 16

Blind the participant as to which intervention they are receiving

Question 17

How can ascertainment bias be minimized during delivery of intervention?

Answer 17

Blind the individuals who administer the interventions

Question 18

How can ascertainment bias be minimized during assessment of outcomes?

Answer 18

Blind the individuals who record the outcomes

Question 19

How can ascertainment bias be minimized during data analysis/ manuscript?

Answer 19

Blind the statisticians

Question 20

What is the intention to treat analysis?

Answer 20

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

Question 21

What is the worst case scenario sensitivity analysis?

Answer 21

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

Question 22

What is the opposite of the intention to treat analysis?

Answer 22

Per protocol analysis

Question 23

What can happen when a study doesn’t use intention to treat analysis?

Answer 23

• 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