Interventional studies

Question 1

All interventional studies have

Answer 1

Phases

Question 2

Differentiators of phases

Answer 2

Purpose/focus
Population studied (healthy/diseased)
Sample size
Duration (depends on disease)

Question 3

Pre-clinical stage

Answer 3

“Bench” or animal research

Question 4

Phase 0

Answer 4

1. Assess drug-target actions and possibly pharacokinetics in single or first few doses (first in-human use)
2. Healthy or diseased volunteers
3. Very small sample size (<20)
4. Very short duration (single dose/few days)

Safety and efficacy not seen here

Question 5

Phase 1

Answer 5

1. Assess safety/tolerance and pharmacokinetics of one or more dosages
2. Healthy or diseased volunteers
3. Small N (20-80)
4. Short duration (few weeks)

Question 6

Phase 2

Answer 6

1. Assess effectiveness (continue to assess safety)
2. Diseased volunteers (NO HEALTHY SUBJECTS, may have narrow inclusion criteria)
3. Larger N (100-300)
4. Short to medium duration (few weeks-few months)

Question 7

Phase 3

Answer 7

1. Assess effectiveness and safety
2. Disease volunteers (NO HEALTHY subjects, may expand inclusion criteria)
3. Larger N (500-3000)
4. Longer duration (few months to a year+)
   If company is using study to submit to FDA for approval, it is phase 3

Question 8

Phase 4

Answer 8

Post FDA approval

1. Assess long term safety, effectiveness, optimal use
2. Diseased volunteers (expand selection criteria)
3. Population few hundred to few hundred thousand
4. Wide range of durations

Question 9

Advantages of interventional trials

Answer 9

Can demonstrate causation

Only study designs used by “FDA” for approval process

Question 10

Disadvantages of interventional trials

Answer 10

Cost
Complexity/time
Ethical considerations
Generalizability/external validity

Question 11

Explanatory (pragmatic) trials

Answer 11

Patients can switch drugs in middle of study

Question 12

Simple interventional design

Answer 12

Divides subjects exclusively into 2+ groups
Commonly used to test a single hypothesis at a time
Only ONE randomization step

Question 13

Factorial interventional design

Answer 13

Randomizes subjects into 2+ groups and then further randomizes each group into 2+ sub groups
Used to test multiple hypotheses at same time

Question 14

Pros/cons factorial design

Answer 14

Improves efficiency for answering clinical questions
Increases study sample size
Increases complexity (may be a barrier to recruitment)
Increases risk of dropouts
May restrict generalizability

Question 15

Parallel interventional design

Answer 15

Groups simultaneously and exclusively managed
No switching of intervention groups after initial randomization
All simple/factorial study designs are also parallel

Question 16

Cross-over interventional design

Answer 16

Groups serve as their own control by crossing over from one intervention to another during study
-allows for smaller total N

Question 17

Run-in/Lead-in phase

Answer 17

Before study begins
All study subjects blindly given one or more placebos for initial therapy to determine a "new" base-line of disease
-Can assess study protocol compliance
-Can wash out existing medication
-Can determine amount of placebo effect

Question 18

Disadvantages of cross over design

Answer 18

Only suitable for long term conditions which are not curable or which treatment provides short-term relief
Duration of study for each subject is longer
Carry-over effects during cross over (wash-out required)
Complexity in data analysis
Smaller N requirement only applicable if within-subject variation less than between-subject variation

Question 19

Patient oriented end points

Answer 19

Death
Stroke
Hospitalization

Question 20

Disease oriented end points

Answer 20

Blood pressure

Cholesterol

Question 21

Table 1 customarily used to

Answer 21

Show group characteristics

Question 22

Blocked randomization

Answer 22

Ensures balance within each intervention group

-when researches want to assure that all groups are equal in size

Question 23

Stratified randomization

Answer 23

Ensures balance with known confounding variables (i.e., gender, age, race)

Question 24

Single blind masking

Answer 24

Study subjects not informed what group they are in but researcher know

Question 25

Open label

Answer 25

No masking/blinding

Question 26

Double-dummy

Answer 26

More than one placebo is used

Question 27

Post-hoc sub-group analysis

Answer 27

No considered appropriately if not prospectively planned

Question 28

Intention to treat

Answer 28

Way of managing drop-outs

• use last known observation for all subsequent, yet missed assessments
• convert all subsequent yet missed assessments to a null-effect (no benefit)

Question 29

Intention to treat results in

Answer 29

Preserves randomization process
Preserves baseline characteristics and group balance at baseline
Maintains statistical power

Question 30

Techniques to manage drop-outs

Answer 30

Intention to treat
Ignore them - Per protocol or efficacy analysis
Treating them “as treated” - allow subjects to switch groups and be evaluated in whichever one they are iin

Question 31

Impact of Per-protocol technique

Answer 31

Biases estimates of effect- commonly overestimates

Reduces generalizability

Question 32

Methods of assessing compliance

Answer 32

Drug levels
Pill counts at each visit
Bottle counter tops

Question 33

Methods of improving compliance

Answer 33

Frequent follow ups
Treatment alarms
Medication blister packs/dosage containers