Interventional Studies (Lecture 2) Flashcards
Systematic Reviews
Report on several studies all combined into one (summarized)
Meta-Analyses
Analyzing the data from multiple studies
Pre-Clinical
Bench or animal research; prior to human investigation
Phase 0
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)
Phase 1
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)
Phase 2
Assess effectiveness and safety/tolerability, diseased volunteers, larger population size (100-300), short to medium duration (a few weeks to a few months)
Phase 3
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)
Phase 4
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)
Pros and Cons of Interventional Studies
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)
Exploratory Study
1 treatment per group; no changing groups, treatments, drugs
Explanatory (Pragmatic) Study
More flexible in their design; can change treatments or drugs between groups; more clinical type approach
Simple Study Design
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
Factorial Study Design
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
Parallel Study Design
Groups simultaneously and exclusively managed; no switching of intervention groups after initial randomization; all simple and factorial study designs are also parallel
Cross-Over (Self-Control) Study Design
Groups serve as their own control by crossing over from one intervention to another during the study
What combinations can interventional studies be?
Simple, Parallel
Simple, Cross-Over
Factorial, Parallel
Factorial, Cross-Over
Wash-Out
Time between leaving first treatment group in a study and entering second group in the study`
Lead-In
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
Disadvantages of Cross-Over Design
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
Primary Outcomes
Most important, key outcomes; main research question used for developing/conducting study
Secondary/Tertiary/etc. Outcomes
Lesser importance yet still valuable; possible for future hypothesis generation
Composite Endpoint
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
Patient Oriented Endpoints
Most clinically relevant; death, stroke, heart attack, hospitalization, preventing need for dialysis
Disease Oriented Endpoints
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)
