Interventional Studies Flashcards
What are some other terms that can be used for interventional studies?
- Clinical trial
- Clinical study
- Experimental study
- Human study
- Investigational study
Key difference between interventional and observational studies
- Can show causation
- investigator selects interventions and allocates study subjects to forced intervention groups
What are the different aspects that determine the different phases of interventional studies?
- Purpose/Focus
- Population studied (healthy/diseased)
- Sample size
- Duration
What does the duration of the study depend on?
- the disease or the research question being asked
What is the purpose of the pre-clinical stage?
- helps drive the hypothesis
Phase 0
- Asses drug-target actions and pharmacokinetics in non-therapeutic/non-diagnostic doses
- Healthy volunteers (or cancer patients)
- Very small (<20)
- Very short duration (single dose to a few days)
Phase 1
- Asses safety/tolerance and pharmacokinetics of one or more dosages
- Healthy or disease volunteers (depending on disease)
- Small (20-80)
- Short duration (a few weeks)
What are some aspects of pharmacokinetics?
- Absorption
- Distribution
- Metabolism
- Excretion
Phase 2
- Asses effectiveness (while still looking at safety and tolerability)
- Diseased volunteers
- Larger N (100-300)
- Short to medium duration (few weeks to a few months)
Phase 3
- asses effectiveness (safety and tolerability as well)
- diseased volunteers
Uses the different perspectives - Larger N (300-500)
- Longer duration (few months to a year)
Phase 4
- post FDA approval
- Assess long term safety, effectiveness and optimal use (risks/benefits)
- Diseased volunteers (comorbidities)
- population N (100,000 - millions)
- Longer duration (many years to decades)
Advantages of Interventional Trials
- Cause precedes effect (can demonstrate causation)
- Only design-family used for FDA approval process
Disadvantages of Interventional Trials
- Cost
- Complexity/Time
- Ethical considerations
- Generalizability
Simple Interventional studies
- Divides (randomizes) subjects once
- Tests a single hypothesis at a time
Factorial Interventional Studies
- Divides (randomized) into groups and then further sub-divides each of the groups into additional sub-groups
- Used to test multiple hypotheses at the same time
What are some characteristics of factorial interventional studies?
- Improves efficiency for answering clinical questions
- Increases study population sample size
- Increases complexity (which may be a recruitment barrier)
- Increases risk of drop outs
- May restrict generalizability results
Parallel Interventional Studies
- groups simultaneously and exclusively manages
- no switching of intervention groups after initial randomization
- All simple and factorial study designs are also parallel
Cross-Over (Self-Control) Interventional Studies
- Groups serve as their own control by crossing over from one intervention to another during the study
- Allows for smaller sample size
What is a washout period?
Refers to the break that happens after a certain time frame in a crossover study. Before the groups are switched.
Run-In/ Lead-in Phase
- determining a new baseline
- cleaning out and baseline establishment before a study starts
Can also be a practice and dry run before the actual study
Disadvantages of Cross-Over Design
- only suitable for long term conditions that are not curable or which treatment provides short term relief
- Duration of study for each subject is longer
- Carry-over effects during crossover
- Treatment-by-period interaction
- Smaller N requirement only applicable if within-subjects variation less than between-subjects variation
- Complexity in data analysis
Primary Outcome
- Most important, key outcome
- Main research question for developing/conducting study
Secondary/Tertiary etc. Endpoints
- Lesser importance but still valuable
- Possible for future hypothesis generation
E.g. Side Effects
Composite Endpoints
- Combines multiple endpoint into a single outcome
Can also be called group outcome