Interventional Study Designs Flashcards
Explain where Interventional (exploratory) and pragmatic (explanatory) studies are in the research evidence pyramid and why they are ranked so highly.
They are both found at the same level, 2nd from the top of the pyramid
both of these study types control the exposure so tightly, that any change in outcome that we see must be very likely to be due to the controlled exposure
What is the main difference of Interventional studies when compared to observational studies? what is useful about this difference?
the investigator selects “interventions” AND allocates study subjects to forced-intervention groups
this more “rigorous” design allows interventional studies to demonstrate causation
List the 4 general differentiators of interventional studies.
- Purpose of the study
- The population being studied (healthy/diseased)
- Sample Size
- Duration of the study/observation
describe Phase 0 interventional studies in terms of “purpose, population, sample size, and duration”
- assess drug-target interactions and possibly pharmacokinetics “does this drug do what we thought it would do?”
- Healthy or diseased volunteers
- very small SS (<20 and usually <12)
- very short duration (single dose to a few days)
Phase 0 are exploratory (used to investigate new drugs)p
Describe interventional study designs
forced allocation into groups occurs, and randomization is usually used to accomplish this. Able to prove causation but can be less ethical
Describe observational study designs
researchers observe subjects occurring naturally or subjects that freely agree to be observed in a study. Cannot prove causation, and there is NO forced group allocation
state, in increasing order of level of evidence, the Inerventional and observational study design types (5 each)
Interventional: Phase 0 through phase 4
Observational: Case reports/series, Ecological, Cross sectional, case-control, and cohort
Describe Preclinical interventional clinical trials
(prior to human investigation) “bench” or animal research
Describe phase 0 interventional clinical trials in terms of they type of study, the main aspect of the exposure being studied, the type of subjects, the sample size, and the length of the study.
Exploratory
assesses drug-target actions/pharmacokinetics in single or few doses (first human testing)
Healthy (sometimes diseased) volunteers
Small N (less than 20)
Short duration
Describe phase 1 interventional clinical trials in terms of they type of study, the main aspect of the exposure being studied, the type of subjects, the sample size, and the length of the study.
Investigational (NOT testing effectiveness yet)
Assess safety/tolerance (all tests after this test safety too) and pharmacokinetics in a “few doses”
Healthy or diseased volunteers
Small N (20-80)
Short duration (a few weeks)
Describe phase 2 interventional clinical trials in terms of they type of study, the main aspect of the exposure being studied, the type of subjects, the sample size, and the length of the study.
Investigational
Assess effectiveness of drug
Diseased volunteers only (may narrow inclusion criteria for this phase)
Larger N (100-300)
Short-to-Medium duration (few weeks/months)
Describe phase 3 interventional clinical trials in terms of they type of study, the main aspect of the exposure being studied, the type of subjects, the sample size, and the length of the study.
Investigational (Indication/Population) last phase before FDA approval
Assess effectiveness, safety and tolerability
Diseased volunteers (may expand inclusion criteria and comparison groups for a delineation of effect)
Statistical perspectives are taken here (superior/noninferiority/equivalency)
Larger N (500-3000)
Longer duration (few months to a year or more)
Describe phase 4 interventional clinical trials in terms of they type of study, the main aspect of the exposure being studied, the type of subjects, the sample size, and the length of the study.
Post-FDA approval
Assess long-term safety/effectiveness and optimal use (risk/benefits)
Diseased volunteers (expands use criteria to delineate long-term saftey/effects)
Population N (few hundred to few thousand)
Wide-range of durations (depends on the drug being tested)
What are the advantages of interventional clinical trials?
The cause precedes the effect and therefore demonstrates causation
These are the only study designs that the FDA uses to “approve” of drugs
What are the disadvantages of interventional clinical trials?
Costly, complex, and time consuming
Ethically questionable issues may arise
Generalizability/external validity is brought into question (how applicable is this data to the real world?)
Explain why interventional clinical trials can prove causation
The cause precedes the effect, and can therefore proves causation? And the study environment is also controlled by this study (so all other exposures/environtment are controlled for as well)
Describe and give an example of Simple study design. also list and advantage and disadvantage of this study design type
randomly divides subjects exclusively into no more than 2 groups and is commonly used to test a single hypothesis ex. One placebo group and one treatment group
Advantages: simple
Disadvantages: only tests one question at a time
Describe and give an example of Parallel study design. also list an advantage and disadvantage of this study design type
NO switching occurs after the initial randomization occurs ex. All simple and factorial designs are also parallel
Advantages: there cannot be confounders due to exposure to a different drug/treatment, like in cross-over studies and it takes less time to complete
Disadvantages: answers fewer questions than other studies
Describe and give an example of Factorial study design. also list an advantage and disadvantage of this study design type
randomly Divides subjects into more than 2 groups and then further divides subjects into more than 2 sub-groups. Used to test multiple hypotheses at once ex. (has several types that are represented by the numerical representation of the groups and sub-groups ex. 2x2, 3x3x2)
Advantages: improves efficiency for answering clinical questions and increases the study population size(out of necessity due to the larger # of groups)
Disadvantages: increases complexity (which may be a barrier to recruitment and increased the risk of drop-outs) and it may restrict the generalizability of the results
Describe and give an example of Cross-Over study design. also state an advantage and disadvantage of this study design type
(self control studies) serve as their own control group by “crossing-over” groups once the study has begun.
Advantages: allows for smaller N values because each subject provides more data than in other studies
Disadvantages: time consuming, washout’s can be messed up, and confounding subjects contribute more data and therefore more confounding
differentiate between primary, secondary, and composite outcomes
Primary: the most important outcome, which answers the hypothesis that was used to develop/conduct the study
Secondary/Tertiary/etc: Less important than primary outcome, but can be used to form possible future hypothesis by which further studies can be conducted
Composite: Combines multiple endpoints into a single outcome
(this could be considered the primary outcome, and if that is the case then the secondary outcomes may be the individual outcome elements from composite)
Compare and contrast patient-oriented endpoints and disease-oriented outcomes. give some examples of both
Patient-Oriented Endpoints (POEM’s): are the most clinically relevant (patients care about these)
Ex. Death, stroke, MI, Hospitalization, and preventing the need for dialysis
Disease-oriented Endpoints (DOE’s): “surrogate outcomes” used in place of evaluating POEM’s
ex. Blood pressure (risk of stroke), Cholesterol (risk for MI), and Change in SCr (risk for worsening renal functioning)
What are the 2 most common general forms of group allocation procedures, when conducting an interventional clinical trial. give examples of each.
Nonrandom: subjects DON’T have an equal probability of being assigned to each group.
Ex. Morning clinic subjects and evening clinic subjects represent the 2 groups OR the first 100 patients admitted to the hospital representing a group
Random: Subjects DO have an equal probability of being assigned to each group
ex. Random-number generating programs
Define randomization and explain how it can yield variable results
Randomization: any method used to make the probability of landing in a group as EQUAL as possible
Even when randomization is used, the equality of the groups is not guaranteed and could potentially have very unequal results. Studies have to document the equalization of the groups by referencing their p value in some way
What are the 3 randomization types that can be utlized by researchers?
simple, blocked, and stratified
Describe simple randomization methods
Simple: equal probability for allocation within one of the study groups
Describe blocked randomization methods
Blocked: ensures balance between each intervention group (creates groups of equal sizes)
Describe stratified randomization methods
Stratified: ensures balance with known confounding variables between groups, and can even pre-select the level of stratification that is desired (not exactly random)
Compare and contrast simple and double blind methods
Single-Blind: study subjects do not know which intervention group they are in, but investigators DO know
Double-Blind: Both the subjects and the investigators do not know which intervention group the subjects are in
Post-study surveys are often used to assess exactly how adequate the blinding protocol was
Describe Placebo/Dummy treatment when it come’s to it’s associate with conducting an interventional clinical trial study
inert (placebo) treatments are made to look identical in all aspects to the active treatments in dosage form, frequency, monitoring, therapy requirements, and so on
Describe Double-Dummy treatment when it come’s to it’s associate with conducting an interventional clinical trial study
more than 1 placebo is used but still given the “dummy treatment”
Describe Placebo-effect when it come’s to it’s associate with conducting an interventional clinical trial study
improvement in condition by the power of suggestion of being “treated” that can be as large as 30-50% (sugar pills example)
Describe Hawthorne-effect when it come’s to it’s associate with conducting an interventional clinical trial study
study subjects change their behavior solely due to their awareness of being studied/observed
Describe Run-in/Lead-in phase when it come’s to it’s associate with conducting an interventional clinical trial study
a period of time that occurs BEFORE the study begins and is often used as a “practice” period where researchers can asses the ability of a subject to adhere to the study’s protocols.
Describe Wash-out phase when it come’s to it’s associate with conducting an interventional clinical trial study
a period of time that occurs when crossing subjects over into another group that attempts to return them back to baseline values. Occurs AFTER the study begins
List ways to assess study participant adherence/compliance in an interventional clinical trial.
Use drug levels so that there are multiple useful sites
Conduct pill counts at each visit
Use the “bottle counter-tops”
List ways to improve study participant adherence/compliance in an interventional clinical trial.
Conduct frequent follow-up visits/have good communication methods
Have subjects set treatment alarms/reminders so they don’t forget
Use medication blister packs/dosage containers to help subjects
