Lecture 11 (RCTs)

Question 1

Treatment is:

Answer 1

• any intervention intended to improve the course of a disease after the disease is established.

Question 2

Intervention is:

Answer 2

• an action intended to change the course of disease, ranging from prevention to palliative care at the end of life.

Question 3

RCT definition/summary:

Answer 3

• prospective, interventional, gold standard
• treatment versus placebo — watch outcome

Question 4

Necessary components of a RCT:

Answer 4

• inclusion/exclusion criteria
• stopping rules for clear evidence of harm, efficacy, and benefit
• informed consent

Question 5

Stats of a RCT:

Answer 5

NNT, RR, AR, ARR

Question 6

When NOT to run a RCT:

Answer 6

• Unnecessary: intervention to be test clearly already works
• Inappropriate (unethical)
• Impossible (to randomize and control exposure)
• Inadequate (not best study for question)

Question 7

Effect of randomization:

Answer 7

• controls for confounding through equal distribution of confounders between groups
• larger the sample size, the better chance randomization decreases confounding

Question 8

Stratification:

Answer 8

• stratify by a strong prognostic factor like age or location
• must occur prior to randomization

Question 9

During the maintenance phase (time during intervention), patients may:

Answer 9

• Not have the disease of interest
• Not adhere to treatment
• Cross-over
• Co-intervention

Question 10

Cross-over:

Answer 10

• when patients take the other group’s treatment during follow-up
• reduces observed treatment effect

Question 11

Co-intervention:

Answer 11

• patients take other treatment besides the one being studied
  
  • can be a problem if patients and physicians are not blinded

Question 12

Four levels of blinding:

Answer 12

• allocation concealment
• single blind - patients
• single blind - physicians
• double blind - patients and physicians

Question 13

Allocation concealment:

Answer 13

• clinicians and investigators who are entering subjects don’t know which group the patient will be in.
• Reduces selection bias.

Question 14

Types of RCT outcomes:

Answer 14

• primary: main hypothesized outcomes
• secondary: too many may cause Type 1 error - multiple comparisons
• composite outcomes: evaluate each component of study

Question 15

Efficacy definition:

Answer 15

does treatment work under ideal conditions?

Question 16

Effectiveness definition:

Answer 16

does treatment work in the real world?

Question 17

Intention-to-treat analysis:

Answer 17

• analyze patients/groups by original randomization regardless of what patient did.
• preserves original randomization
• will bias toward the null - we accept this to avoid type 1 error by other confounders.

Question 18

Explanatory (per protocol) analysis:

Answer 18

• analyze only patients who completed protocol requirements.

Question 19

Superiority trial:

Answer 19

• is one treatment better than the other?

Question 20

Equivalence trial:

Answer 20

• is new treatment better or worse than the reference/current treatment?
  
  • both directions (better or worse)
  • uses inferiority margin

Question 21

Non-inferiority trial:

Answer 21

• is new treatment not worse than reference/current treatment?
  
  • one direction (the same/better)
  • non-inferior treatments may be chosen when they have less side effects, are less invasive, easier to use, cheaper, etc.
  • uses inferiority margin

Question 22

Cluster RCT:

Answer 22

• naturally occurring groups are randomized together as a unit
  
  • i.e. all patients in a single hospital get put into the same group

Question 23

Cross-over RCT:

Answer 23

• each patient gets all the treatments in random order after a suitable wash-out period

Question 24

Number needed to treat (NNT) equation and table:

Answer 24

• takes everyone into account
• NNT = 1/ARR

Question 25

Absolute risk reduction equation and table:

Answer 25