Interventional Study Design

Question 1

Interventional study designs are considered non random, T or F?

Answer 1

False they are randomized to decrease selection bias

Question 2

What are other names for interventional studies?

Answer 2

Human study, Clinical Trial, Investigational study, Experimental Study

Question 3

What are the four differentiators in Interventional studies?

Answer 3

Purpose/Focus Population studied- early phases are more likely to include healthier patients Sample size- increases as phase increases Duration of study

Question 4

What is the key difference in interventional studies and observational studies?

Answer 4

Participants are forcibly allocated into groups

Question 5

T or F Do interventional studies demonstrate causation?

Answer 5

Yes

Question 6

Describe a phase 0 study.

Answer 6

Exploratory Look at drug target actions, can it reach its receptor and bind? Pharmokinetics in a single or maybe few doses. Very small number and short duration, also healthy volunteers typically

Question 7

What is a preclincal stage?

Answer 7

Before human investigation Bench or animal research

Question 8

What can help demonstrate that a study is phase 0?

Answer 8

If the name contains random letters and numbers ex: AZD1775 also single dose

Question 9

Describe a phase 1 study.

Answer 9

Assess safety/tolerability and pharmocokinetics of 1+ doses in humans. Can have healthy or diseased subjects depending on disease. Small number 20-80 ish Short duration

Question 10

Describe phase 2 study.

Answer 10

Assess effectiveness as well as safety/tolerabilty Only diseased volunteers- narrow inclusion exclusion Larger number few weeks to few months

Question 11

Phase 3 study.

Answer 11

Continue to assess safety/tolerability effectiveness Diseased volunteers- expand inclusion criteria and comparison groups Can take statistical standpoints Larger number several hundred couple thousand Longer duration Before FDA approval.

Question 12

Phase 4.

Answer 12

Post FDA approval assess long term effects diseased volunteers less inclusion expand criteria bc on marker- comorbidities and contaminant medications Population number large Wide ranges of time.

Question 13

What study design is used for FDA approval?

Answer 13

Interventional Study

Question 14

What are the disadvantages to Interventional trials?

Answer 14

Cost complexity time ethical considerations generalizability (external valididty)

Question 15

Simple Interventional Study?

Answer 15

Randomizes subjects into two groups

one level of randomization

Question 16

What are simple interventional studies used for?

Answer 16

To test one hypothesis at a time

Question 17

What is a factorial study design?

Answer 17

Randomizes subjects into two grpups and then a second level of randomization into additional subgroups

Question 18

What is a factorial study used for?

Answer 18

Testing multiple hypotheses at the same time

Question 19

What are the pros and cons to factorial study designs?

Answer 19

Improves efficiency for answering clinical questions

Increases study population size

increases complexity which can make it hard to get participants

Increases risk of drop outs

Can restrict generalizablity

Question 20

What are parallel study designs?

Answer 20

Groups don’t cross into other groups once they have been randomized

Can be simple or factorial

Question 21

what are cross over studies?

Answer 21

Groups act as own controls because they cross over from one group to the other after wash out

Question 22

Run in phase?

Answer 22

Helps asses placebo effects and compliance before study begins as well as wash out existing medication before the study beigns

Question 23

What are disadvantages to Cross over designs?

Answer 23

Only good for long term conditions that aren’t curable or short term relief

Duration is longer becaue participants are going through two studies

Carry over effects

Treatment by period interaction

smaller number can be used because participants will act as controls

complexity within the analysis

Question 24

What are examples of disease oriented endpoints? How does this compare to POEM’s?

Answer 24

Blood pressure number for risk of stroke

Cholesterol number for risk of heart attack

Change in SCr levels (renal fxn)

In patient orienented endpoints you speak in relevance to the patient- such as lowering your blood pressure can decrease your risk of stroke which will decrease your risk of death, hospitalization or other.

Question 25

what is non random group allocation?

Answer 25

Subject do NOT have equal probability of being selected to a group. This would be convenience sampling or quasi systematic.

Question 26

What is random group allocation? What is the purpose of it?

Answer 26

Most utilized form of allocation subjects have an equal probability of being selected to a group. The purpose is to make grpups as equal as possible based on known and unknown factors- an attempt to reduce bias between groups. Equality is NOT gauranteed.

Question 27

What are the types of randomization?

Answer 27

Simple

Blocked

Stratifed

Question 28

What is simple randomiztion?

Answer 28

Equal probability of allocation within one study gorup

Question 29

What is blocked randomization?

Answer 29

Ensures balance within each intervention grpup- for when researchers want to assure all groups are equal in size

Question 30

What is stratified randomization?

Answer 30

Ensures balance with known confounding variables such as age gendeer disease severity and length or comorbidities

Question 31

What is a single blind study?

Answer 31

Study subjects dont know hwat group they are in but investigators do

Question 32

What is a double blind study?

Answer 32

Neither investigators or subjects know what they are getting. This reduces the risk of biases.

Question 33

What are unmasked/ open label/ unblinded studies?

Answer 33

Subjects and researches know what is being receivedd?

Question 34

What are post hoc surveys used for?

Answer 34

Assessing the adequacy of blinding

Question 35

When is a post hoc study acceptable?

Answer 35

When is is prospecituvely planned. NOT done on a whim, that is known as “data dredging or fishing”

Question 36

How do you manage LTF in your statistical analysis?

Answer 36

You can include them anyways- Intention to treat which is the most conservative decision. You use their last collected assessment. This preserves randomization, baseline characteristics and group balance and maintains statistical power (same size groups). OR you don’t include them-Per-Protocol or Efficacy-Analysis. Complicance must be predefined in these cases. OR Treat them “as treated”. Ignoring the group assignments allows subjects to switch gourps and be evaluated in the group they moved to or were in longest.

Question 37

Impact of Per-Protocol?

Answer 37

Commonly over estimated effects, reduces generalizability

Question 38

What are ways to assess adherence or improve adherence?

Answer 38

Pill counts, bottle counter tops, drug levels

Improve with frequent communication and follow ups treatment alarms or notifications medication blister packages or dosage containers

Question 39

What are advantages and disadvantages of Interventional trials?

Answer 39

Demonstrates causation!!

Key design for FDA approval

Cost

Complexity

Ethics

Generalizabilty- External validity

Question 40

What are pros and cons to factorial interventional study designs?

Answer 40

Improves efficiency for answering hypothesis

Increases sample size

Increases complexity- could hurt recruitment

Increase risk of drop out due to complexity

Could restrict generalizibilty