DI

Question 1

What is Validity

Answer 1

Degree measurement represents true value

Question 2

What is Reliability

Answer 2

Reproducibility of measurement

Question 3

Subjective Outcomes

Answer 3

Likert Scales

Self-reported symptoms

Question 4

Objective Outcomes –

Continuous Data

Answer 4

• Lab values
• BP
• Weight

Question 5

Objective Outcomes –

Nominal Data

Answer 5

• Death (yes/no)
• ED admit count
• MI

Question 6

what is Minimal Clinically Important Difference (MCID)

Answer 6

Amount of improvement that is important to patients

Question 7

Methods to determine MCID

Answer 7

• Expert consensus
• Anchor to independent categorical assessment scores
• Distribution-based method relies on the statistical properties of the distribution of outcome

Question 8

Outcomes Important to Patients

Answer 8

Pain scales, depression scores

Delayed or reduced rates of death

Reduced hospitalizations or disease incidence

not lab valves

Question 9

What is a surrogate endpoint

Answer 9

”A laboratory measurement or physical sign that is used in therapeutic trials as a substitute for a clinically meaningful end point that is a direct measure of how a patient feels, functions, or survives, and that is expected to predict the effect

of therapy.

Question 10

common Surrogate

Answer 10

Osteoporosis
• BMD
Cardiovascular
• LDL cholesterol 
• LV Ejection fraction 
• Blood pressure 
• Premature ventricular 
contractions (PVCs)

Question 11

Clinically Meaningful Endpoints

Answer 11

Osteoporosis
•Fractures
Cardiovascular
• CV death, MI, stroke 
• HF survival 
• CV death, MI, stroke 
• Fatal arrhythmia, sudden death

Question 12

Surrogate Endpoints Disadvantages

Answer 12

Trial too short to evaluate 
long-term side-effects
• Patients don’t relate their 
clinical experience to surrogate
• Intervention may affect 
surrogate endpoint but not clinical outcome

Question 13

Surrogate Endpoints Advantages

Answer 13

• Smaller sample size;
expose fewer patients
• Shorter trials / faster to market
• Easier to measure • Less invasive for patients

Question 14

Surrogates are justified for

Answer 14

• Rare diseases (familial hypercholesterolemia)

* Slow developing but fatal diseases with no effective therapy (AML)

Question 15

Composite Outcome Definition

Answer 15

• Combination of two or more related “component” outcomes
• Patients are
counted once if any of the
“component” outcomes occurs

Question 16

Composite Outcome Disadvantages

Answer 16

• Can be misleading if the
treatment effect varies across the components and components have unequal importance
• Can be difficult to interpret

Question 17

Composite Outcome Advantages

Answer 17

• Improves statistical power 
(i.e. smaller samples)
• Allows use of multiple, 
similar outcomes (don’t 
have to choose)

Question 18

validity of composite outcomes

Answer 18

depends on similarity

in patient importance, treatment effect and incidence across the components.

Question 19

P-values

Answer 19

• Indicates precision in the 
abstract (i.e. rejecting the null). 
• Does NOT provide good 
indication of variability.
• Does NOT provide any 
indication of clinical significance.
• Less desirable

Question 20

Confidence Intervals (CI)

Answer 20

• Indicates precision in the 
abstract (i.e. rejecting the null). 
• Indicates variability (i.e. 
wideness of interval)
• Provides information 
about clinical significance
• More desirable

Question 21

Alpha (Type I) error

Answer 21

Inconsistent with other findings and wide variation

OR
• Inconsistent with other findings and close to null

Question 22

Type 2 (beta) error

Answer 22

Narrow CIs (little variation) but “touches” the null
AND Effect size within MCID
• Look for consistency with other findings

Question 23

Superiority Trial

Answer 23

New drug (e.g. Prilosec™) better than old drug (H2A) or placebo

Question 24

Non-inferiority Trial

Answer 24

New drug (e.g.  Nexium™) is no worse than old drug (e.g. Prilosec™) 
• No worse than a preset margin

Question 25

Equivalency Trial

Answer 25

New drug (e.g. generic omeprazole)
“equivalent to old drug (e.g. Prilosec™)
• No worse AND no better than a preset

margin

Question 26

delta (D)

Answer 26

clinically acceptable difference

D usually established from
pooled placebo controlled trials

• Treatments with CIs within the D are said to be “non-inferior” or “equivalent”