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)
Non-Random Group Allocation
Subjects don’t have an equal probability of being selected or assigned to each intervention group
Random Group Allocation
Most common; subjects do have an equal probability of being assigned to each intervention group
Purpose of Randomization
Make groups as equal as possible; based on known and unknown important factors (confounders); equality of groups is NOT guaranteed
Simple Randomization
Equal probability for allocation within one of the study groups
Blocked Randomization
Ensures balance within each intervention group; used when researchers want to assure that all groups are equal in size
Stratified Randomization
Ensures balance with known confounding variables such as gender, age, disease severity/duration
Single Blind Study
Study subjects not informed which intervention group they are in, yet investigators are permitted to know
Double Blind Study
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
Open-Label Study
Study subjects and researchers know what intervention is being received
Placebo/”Dummy” Therapy
Inert treatments made to look identical in all aspects to the active treatments
Double Dummy Therapy
More than one placebo used
Placebo Effect
Improvement in condition by power of suggestion of being “treated”
Hawthorne Effect
Study subjects change their behavior solely due to awareness of being studied/observed
Post-hoc Sub-group Analysis
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
Assessing Adherence
Drug levels, pill counts at each visit, bottle counter-tops
Methods of Improving Adherence
Frequent follow-up visits/communications, treatment alarms/notifications, medication blister packs or dosage containers
