Interventional Study Design Flashcards
Interventional study designs are considered non random, T or F?
False they are randomized to decrease selection bias
What are other names for interventional studies?
Human study, Clinical Trial, Investigational study, Experimental Study
What are the four differentiators in Interventional studies?
Purpose/Focus Population studied- early phases are more likely to include healthier patients Sample size- increases as phase increases Duration of study
What is the key difference in interventional studies and observational studies?
Participants are forcibly allocated into groups
T or F Do interventional studies demonstrate causation?
Yes
Describe a phase 0 study.
Exploratory Look at drug target actions, can it reach its receptor and bind? Pharmokinetics in a single or maybe few doses. Very small number and short duration, also healthy volunteers typically
What is a preclincal stage?
Before human investigation Bench or animal research
What can help demonstrate that a study is phase 0?
If the name contains random letters and numbers ex: AZD1775 also single dose
Describe a phase 1 study.
Assess safety/tolerability and pharmocokinetics of 1+ doses in humans. Can have healthy or diseased subjects depending on disease. Small number 20-80 ish Short duration
Describe phase 2 study.
Assess effectiveness as well as safety/tolerabilty Only diseased volunteers- narrow inclusion exclusion Larger number few weeks to few months
Phase 3 study.
Continue to assess safety/tolerability effectiveness Diseased volunteers- expand inclusion criteria and comparison groups Can take statistical standpoints Larger number several hundred couple thousand Longer duration Before FDA approval.
Phase 4.
Post FDA approval assess long term effects diseased volunteers less inclusion expand criteria bc on marker- comorbidities and contaminant medications Population number large Wide ranges of time.
What study design is used for FDA approval?
Interventional Study
What are the disadvantages to Interventional trials?
Cost complexity time ethical considerations generalizability (external valididty)
Simple Interventional Study?
Randomizes subjects into two groups
one level of randomization
What are simple interventional studies used for?
To test one hypothesis at a time
What is a factorial study design?
Randomizes subjects into two grpups and then a second level of randomization into additional subgroups
What is a factorial study used for?
Testing multiple hypotheses at the same time
What are the pros and cons to factorial study designs?
Improves efficiency for answering clinical questions
Increases study population size
increases complexity which can make it hard to get participants
Increases risk of drop outs
Can restrict generalizablity
What are parallel study designs?
Groups don’t cross into other groups once they have been randomized
Can be simple or factorial
what are cross over studies?
Groups act as own controls because they cross over from one group to the other after wash out
Run in phase?
Helps asses placebo effects and compliance before study begins as well as wash out existing medication before the study beigns
What are disadvantages to Cross over designs?
Only good for long term conditions that aren’t curable or short term relief
Duration is longer becaue participants are going through two studies
Carry over effects
Treatment by period interaction
smaller number can be used because participants will act as controls
complexity within the analysis
What are examples of disease oriented endpoints? How does this compare to POEM’s?
Blood pressure number for risk of stroke
Cholesterol number for risk of heart attack
Change in SCr levels (renal fxn)
In patient orienented endpoints you speak in relevance to the patient- such as lowering your blood pressure can decrease your risk of stroke which will decrease your risk of death, hospitalization or other.
what is non random group allocation?
Subject do NOT have equal probability of being selected to a group. This would be convenience sampling or quasi systematic.
What is random group allocation? What is the purpose of it?
Most utilized form of allocation subjects have an equal probability of being selected to a group. The purpose is to make grpups as equal as possible based on known and unknown factors- an attempt to reduce bias between groups. Equality is NOT gauranteed.
What are the types of randomization?
Simple
Blocked
Stratifed
What is simple randomiztion?
Equal probability of allocation within one study gorup
What is blocked randomization?
Ensures balance within each intervention grpup- for when researchers want to assure all groups are equal in size
What is stratified randomization?
Ensures balance with known confounding variables such as age gendeer disease severity and length or comorbidities
What is a single blind study?
Study subjects dont know hwat group they are in but investigators do
What is a double blind study?
Neither investigators or subjects know what they are getting. This reduces the risk of biases.
What are unmasked/ open label/ unblinded studies?
Subjects and researches know what is being receivedd?
What are post hoc surveys used for?
Assessing the adequacy of blinding
When is a post hoc study acceptable?
When is is prospecituvely planned. NOT done on a whim, that is known as “data dredging or fishing”
How do you manage LTF in your statistical analysis?
You can include them anyways- Intention to treat which is the most conservative decision. You use their last collected assessment. This preserves randomization, baseline characteristics and group balance and maintains statistical power (same size groups). OR you don’t include them-Per-Protocol or Efficacy-Analysis. Complicance must be predefined in these cases. OR Treat them “as treated”. Ignoring the group assignments allows subjects to switch gourps and be evaluated in the group they moved to or were in longest.
Impact of Per-Protocol?
Commonly over estimated effects, reduces generalizability
What are ways to assess adherence or improve adherence?
Pill counts, bottle counter tops, drug levels
Improve with frequent communication and follow ups treatment alarms or notifications medication blister packages or dosage containers
What are advantages and disadvantages of Interventional trials?
Demonstrates causation!!
Key design for FDA approval
Cost
Complexity
Ethics
Generalizabilty- External validity
What are pros and cons to factorial interventional study designs?
Improves efficiency for answering hypothesis
Increases sample size
Increases complexity- could hurt recruitment
Increase risk of drop out due to complexity
Could restrict generalizibilty
