What type of study is most commonly read and the only type to prove causation?
Name other terms used for interventional studies
Clinical trial Clinical study Experimental study Human study Investigational study
What are the phases of interventional studies?
Pre-Clinical Phase 1 Phase 2 Phase 3 Phase 4
What phase is prior-to human investigation and is usually associated with bench and animal research?
What phase does this describe? Small population (~20-80) Short duration Safety
What phase does this describe? Population size ~100-300 Safety and Efficacy Short-to-Medium duration (few to several months) Likely to have narrower inclusion criteria
What phase does this describe? Population size ~1,000-3,000 Duration of many months to a year (or few years) Safety, but primarily efficacy
What phase does this describe? Long-term effects Risks and Benefits Large population size Registries/Surveys
What are the advantages of interventional trials (vs. other designs)?
Cause precedes effect (shows causation) Only design used by FDA for "approval" process
What are the disadvantages to interventional studies (vs. other designs)?
Cost Complexity/Time (development/approval/conductance) Ethical considerations (risk vs. benefit eval) **Generalizability (aka External Validity)
What are the disadvantage of an "explanatory" interventional study?
They do not give you flexibility like you normally have in clinical practice They give you an exact playbook on the to play the game and as a clinician, you cannot deviate
How is a "pragmatic" interventional study less restrictive than an "explanatory" interventional study?
Pragmatic studies rarely use placebo More clinically relevant Let in real people, people that have real co-morbidities, people on other meds
What are the disadvantages of "pragmatic" interventional studies?
Researcher loses control of how physicians prescribe/manage patients Might introduce confounding Loss of control and rigidity
Describe a SIMPLE study design
Divides subjects into as many as 2 groups (single randomization process) Commonly used to test a SINGLE hypothesis
Describe a FACTORIAL study design
Divides subjects into two or more groups and then further randomizes Used to test multiple hypotheses at the same time Must increase population size
What are the benefits/disadvantages to a FACTORIAL study design?
Improves efficiency for answering clinical questions Increases study pop. sample size Increases complexity Increases risk of drop outs May restrict generalizability of results
Describe a PARALLEL study design
Groups simultaneously and exclusively managed No switching of intervention groups after initial randomization Includes all simple and factorial study designs
Describe a CROSS-OVER study design
Groups serve as their own control by crossing over from one intervention to another during the study Allows for small total N Each patient contributes additional data Between & Within group comparisons possible
Period needed for groups to get their systems back to baseline
Define Lead-in/Run-in Phase
All study subjects blindly given one or more placebos for initial therapy to determine a "new" base-line of disease. Uses to assess for placebo-effects, Hawthorne-effect, and compliance before study begins
What can we assess/determine from the Lead-in/Run-in phase?
Can assess study protocol compliance Can "wash-out: existing medication Can determine amount of placebo-effect
List the 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 effect (requires wash-out) Treatment-by-period interaction Smaller N requirement only applicable if within-subjects variation less than between-subj. variation Complexity in data analysis
What study format is demonstrated in the graphic?
Describe a Primary Outcome/Endpoint
Most important, ket outcome Main research question (hypothesis) of study
Describe a secondary/tertiary/etc.. outcome/endpoint
Lesser importance yet still valuable Possible for future hypothesis generation
Describe a composite outcome/endpoint
Combines multiple endpoints into a single outcome Could be considered the primary outcome, and if so, then secondary outcome may be the individual outcome elements from composite
Examples of Patient-Oriented Endpoints (most clinically relevant)
Death Stroke or Myocardial Infarction Hospitalization Preventing need for dialysis
Examples of Surrogate Markers (elements used in place of evaluating Patient-Oriented (direct) Endpoints)
Blood Pressure (for risk of stroke) Cholesterol (for risk of heart attack) Change in SCr (for worsening of renal function)
Explain Non-Random sample selection and group allocation
Subjects DO NOT have an equal probability of being selected or assigned to each intervention group (e.g., Convenience Sampling, Non-probabilistic allocation)
Explain Random sample selection and group allocation
Most commonly utilized
Subjects DO have an equal probability of being assigned to each intervention group