Interventional Studies (Lecture 2)

Question 1

Systematic Reviews

Answer 1

Report on several studies all combined into one (summarized)

Question 2

Meta-Analyses

Answer 2

Analyzing the data from multiple studies

Question 3

Pre-Clinical

Answer 3

Bench or animal research; prior to human investigation

Question 4

Phase 0

Answer 4

Assess drug target actions and possibly pharmacokinetics in single or few doses, healthy or diseased patients, very small population size (less than 20), very short duration (a few days)

Question 5

Phase 1

Answer 5

Assess safety/tolerance and pharmacokinetics of one or more dosages, healthy or diseased volunteers, small population size (20-80), short duration (just a few weeks)

Question 6

Phase 2

Answer 6

Assess effectiveness and safety/tolerability, diseased volunteers, larger population size (100-300), short to medium duration (a few weeks to a few months)

Question 7

Phase 3

Answer 7

Last phase before FDA approval; assess effectiveness and safety/tolerability, diseased volunteers and can include comparison groups for delineation of effects, larger population size (500-3000), longer duration (a few months to a year or more)

Question 8

Phase 4

Answer 8

Post FDA approval; assess long term safety, effectiveness, optimal use (risks/benefits), diseased volunteers, very large population size (a few hundred to a few hundred thousand), wide range of durations (a few weeks to several years)

Question 9

Pros and Cons of Interventional Studies

Answer 9

Pros: Cause precedes effect (can demonstrate causation), only designs used by FDA for approval process

Cons: Cost, complexity/time, ethical considerations, generalizability/external validity (is study population similar to general population and will methodology and findings be applicable to them)

Question 10

Exploratory Study

Answer 10

1 treatment per group; no changing groups, treatments, drugs

Question 11

Explanatory (Pragmatic) Study

Answer 11

More flexible in their design; can change treatments or drugs between groups; more clinical type approach

Question 12

Simple Study Design

Answer 12

Divides (randomizes) subjects exclusively into 2 or more groups; single randomization process; no subsequent randomized divisions; commonly used to test a single hypothesis at a time

Question 13

Factorial Study Design

Answer 13

Divides (randomizes) subjects into 2 or more groups and then further sub-divides (randomizes) each of the groups into 2 or more additional sub-groups; used to test multiple hypotheses at the same time

Question 14

Parallel Study Design

Answer 14

Groups simultaneously and exclusively managed; no switching of intervention groups after initial randomization; all simple and factorial study designs are also parallel

Question 15

Cross-Over (Self-Control) Study Design

Answer 15

Groups serve as their own control by crossing over from one intervention to another during the study

Question 16

What combinations can interventional studies be?

Answer 16

Simple, Parallel
Simple, Cross-Over
Factorial, Parallel
Factorial, Cross-Over

Question 17

Wash-Out

Answer 17

Time between leaving first treatment group in a study and entering second group in the study`

Question 18

Lead-In

Answer 18

All study subjects blindly given one or more placebos for initial therapy (defined time-period) to determine a “new” base-line of disease (standardization); can assess study protocol compliance, wash out existing medications, and determine amount of placebo effect

Question 19

Disadvantages of Cross-Over Design

Answer 19

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 which prolongs study duration)

Complexity in data analysis

Question 20

Primary Outcomes

Answer 20

Most important, key outcomes; main research question used for developing/conducting study

Question 21

Secondary/Tertiary/etc. Outcomes

Answer 21

Lesser importance yet still valuable; possible for future hypothesis generation

Question 22

Composite Endpoint

Answer 22

Combines multiple endpoints into a single outcome; could be considered the primary outcome, and if so, then secondary outcomes may be the individual outcome elements from composite

Question 23

Patient Oriented Endpoints

Answer 23

Most clinically relevant; death, stroke, heart attack, hospitalization, preventing need for dialysis

Question 24

Disease Oriented Endpoints

Answer 24

Elements used in place of evaluating patient-oriented endpoints; blood pressure (for risk of stroke), cholesterol (for risk of heart attack), change in SCr (for worsening renal function)

Question 25

Non-Random Group Allocation

Answer 25

Subjects don’t have an equal probability of being selected or assigned to each intervention group

Question 26

Random Group Allocation

Answer 26

Most common; subjects do have an equal probability of being assigned to each intervention group

Question 27

Purpose of Randomization

Answer 27

Make groups as equal as possible; based on known and unknown important factors (confounders); equality of groups is NOT guaranteed

Question 28

Simple Randomization

Answer 28

Equal probability for allocation within one of the study groups

Question 29

Blocked Randomization

Answer 29

Ensures balance within each intervention group; used when researchers want to assure that all groups are equal in size

Question 30

Stratified Randomization

Answer 30

Ensures balance with known confounding variables such as gender, age, disease severity/duration

Question 31

Single Blind Study

Answer 31

Study subjects not informed which intervention group they are in, yet investigators are permitted to know

Question 32

Double Blind Study

Answer 32

Neither investigators nor study subjects are informed which intervention group subjects are in; post study survey’s can be used to assess adequacy of blinding

Question 33

Open-Label Study

Answer 33

Study subjects and researchers know what intervention is being received

Question 34

Placebo/”Dummy” Therapy

Answer 34

Inert treatments made to look identical in all aspects to the active treatments

Question 35

Double Dummy Therapy

Answer 35

More than one placebo used

Question 36

Placebo Effect

Answer 36

Improvement in condition by power of suggestion of being “treated”

Question 37

Hawthorne Effect

Answer 37

Study subjects change their behavior solely due to awareness of being studied/observed

Question 38

Post-hoc Sub-group Analysis

Answer 38

Not accepted as appropriate, by most, when NOT prospectively planned (increases risk of Type 2 error); Is accepted as appropriate, by most, when it is prospectively planned, or performed for hypothesis generation and development of future studies

Question 39

Assessing Adherence

Answer 39

Drug levels, pill counts at each visit, bottle counter-tops

Question 40

Methods of Improving Adherence

Answer 40

Frequent follow-up visits/communications, treatment alarms/notifications, medication blister packs or dosage containers