2.2 Interventional Study Designs Flashcards
What are the two differences between interventional studies and observational?
Interventional does forced group allocation and demonstrates causation
What are the 5 interventional studies?
Phase 0,1,2,3,4
What are we looking for in the difference between these studies?
Purpose, population studies (diseased/not), sample size and duration
What is the purpose to Phase 0?
Exploratory, investigational new drug. Assess drug target actions and possibly pharmacokinetics in a single or few doeses
What is the population study in Phase 0?
Healthy.
What is the population size in Phase 0?
Small like 20 or so.
What is the duration of Phase 0?
Very short, few days.
What is the purpose of Phase 1?
Investigational New drug. Safety and tolerability. Where it goes how it metabolizes. How does the body handle the drug?
What is the population study in Phase 1?
Healthy or diseased
What is the population size in Phase 1?
Small like 20-80 sometimes.
What is the duration in Phase 1?
Short. Few weeks.
What is the purpose for Phase 2?
Investigational New drug. Assess effectiveness (continue to assess safety tolerability).
What is the population study in Phase 2?
Diseased
What is the population size in Phase 2?
Large around 100-300.
What is the duration in Phase 2?
Short to medium. few weeks to a few months
What is the purpose in Phase 3?
Investigational New drug, Indication/population. Assess effectiveness but with more people.
What is the population study in Phase 3?
Diseased. Supriority, noninferiority, and equivalency.
What is the population size in Phase 3?
Large. 500-3000
What is the duration in phase 3?
Long. Few months to a year.
What phase is the last phase before FDA approval?
Phase 3
What is the purpose in Phase 4?
Pose FDA approval. Assess long term safety, effectiveness.
What is the study population in Phase 4?
Diseased,
What is the population size in Phase 4?
Large. few hundred to a few thousand.
What is the duration in Phase 4?
Ranges from few weeks to several years, ongoing.
What are the 2 advantages of interventional studies?
Demonstrates causation, and only designs used by FDA for approval.
What are the disadvantages of interventional studies?
Cost, complex, Ethical considerations, and EXTERNAL validity.
What are exploratory studies?
Answer the research question, explore the if the drug is effective. Great for proving causation but external validity is bad
What are Pragmatic studies?
More flexibility for researchers. We can lose precision of controlling. Confounders.
What are the 4 designs of interventional studies?
Simple, Factorial, Parallel, and Cross over
What is Factorial intervenitonal study design?
Divides (Randomizes) subjects into 2 or less groups and then further sub-divides each othe groups into less than 2 addional sub groups
What is the Factorial study design used to test?
Multiple hypotheses at the same time.
What are 5 things that Factorial study design can do?
Improves efficiency for answering clinical questions. Increases study population sample size. Increases complexity. Increases risk of drop outs. May restrict generalizability of results.
What is Simple study design?
Divides randomizes subjects into less than 2 groups.
What is used to test in a simple Study design?
Single hypothesis
What is Parallel study design?
A study on which pts are in a group they need to be in they stay in that group for the rest of the study. Can not switch groups.
True or false? All simple and Factorial study designs are not Parallel
False. They are all parallel.
What is the cross over study design?
Is a study that allows pts to be treated in one group and switch into another study. A crossover in a graph will always have an arrow that crosses over in a study meaning that pts can cross over.
What is wash-out pertaining to crossover period?
washout which means a period of time on the calendar that we are not giving pts any treatments we want the old effects in the first group to get out of their system.
What is the Lead in phase pertaining to crossover period?
there are studies that pts have a disease and their doc is treating them that such that study wont let them be on the drugs before they can start. We tend to use the before the study starts called LEAD IN phase.
What are the disadvantages of cross over?
Suitable for long term conditional only that arnt curable or treatment only provides a short term relief. Complex data. Duration of study longer. carry over effects during cross over. Smaller N requirement.
What are the 3 outcomes endpoints to interventional study designs?
Primary, Secondary and composite
What is the primary outcome?
Most important key outcome
What is the secondary outcome?
Less importance
What is the composite outcome?
Combines multiple endpoints into a single outcome
What are some examples inf patient orientated endpoints (POEMS)?
Death, stroke. MI, hospitalization.
What are some examples of disease oriented endpoints (DOEs)?
Blood pressure, cholesterol, change in SCr
What is non random group allocation?
Subjects dont have an equal prob of being selected or assigned to each intervention group.
What is random group allocation?
Most common, subjects do have an equal probability of being assigned to each intervention group.
What is the purpose of randomization?
To make groups as equal as possible based on known and unknown important factors (cofounders).
During randomization what is no guaranteed?
Equality of groups
What are 3 forms of randomization?
Simple, blocked and stratified
What is simple pertaining to randomization?
Equal prob for allocation within one of the study groups
What is blocked pertaining to randomization?
Ensures balance within each intervention group. ex: every 10th pts we are going to stop and take a peak of the groups so that they are unequal we will be more heavy handed on the others. Like if we are flipping the coin and its like 6 to 2, we are putting the other pts in the low number.
What is stratified pertaining to randomization?
Ensures balance with known confounding variables. Ex: gender age, disease.
What are the three masking types?
Single-blind, double-blind, and open-label
What is single blind?
Subjects not informed which intervention group they are in. Researchers are permitted to know
What is Double blind?
Neither researchers nor study subjects know which intervention group the subjects are in
What is open label?
Subjects and researchers know what intervention is being received.
What are the 2 forms of blinding?
Placebo and double dummy
What is placebo?
Inert treatments made to look identical in all aspects to the active treatments
What is double dummy?
more than 1 placebo used
What is the placebo effect?
Improvement in condition by power of suggestion of being treated
What is the Hawthorne effect?
study subjects change their behavior sue to their realization that they are being watched
What are two things you can do when dealing with drop outs/lost to follow ups?
Ignore them or treat them as treated
What are 3 ways to assess complicance of pts?
Drug levels, pill counts at each visit and bottle counter tops
What are 3 ways of improving compliance of pts?
Frequent follow up visits, treatment alarms, medication blister packs or dosage containers.
