Interventional Study Designs Flashcards
What study designs are thought to be the only ones that can prove causation?
interventional studies
What are some other terms for interventional studies?
clinical trial, clinical study, experimental study, human study, investigational study
What is the key difference between interventional and observational studies?
In interventional, investigator selects interventions and allocates study subjects to forced-intervention groups. They are more “rigorous” in ability to demonstrate causation.
What is the pre-clinical phase of an interventional study?
study phase that does NOT involve humans; it may involve animals.
In general, the higher the phase, the higher the _____
population.
What is phase 1 of an interventional study?
phase in which healthy volunteers (20 - 80) are used to asses safety, dose, toxicity of a drug. It is a short duration.
What is phase 2 of an interventional study?
phase in which 100 - 300 patients with condition of interest are used to determine efficacy; safety is still important. It is short to medium in duration.
What is phase 3 of an interventional study?
Phase in which 1000 - 3000 patients with condition of interest are tested, with a PRIMARY purpose of efficacy. It also uses superiority, non-inferiority and equivalency formats.
What is another word for placebo?
Dummy
What is phase 4 of an interventional study?
Long term effects of a drug in a large population are assessed. The goal is maintain long-term safety. It may rely on registries and surveys and can also be considered an observational study.
What kind of study is phase 4 sometimes considered to be?
observational
What are the advantages of interventional trials?
they can show causation and they are the only studies used by the FDA.
What are the disadvantages of interventional trials?
cost, time, ethics, and most importantly external validity - are the conditions of the study applicable to the general population?
What is a feature of explanatory studies?
they are generally restrictive in the amount of dosages, etc. given to each patient. They do not have much flexibility.
What is a feature of pragmatic studies?
they are more flexible - drug combinations may be compared, placebos may not be used, and regulat people with multiple comorbidities are studied.
What is a simple interventional study?
A study in whcih patients are randomized only once. Patients are divided into two groups, and a single hypothesis is tested.
What is a factoral interventional study?
A study in which subjects are randomized at least twice; groups are divided into sub-groups. It is used to test multiple hypotheses at the same time.
What is a negative of a factorial study?
More participants are needed in order to answer more questions.
What are benefits of a factorial study?
Efficiency, sample size, complexity are improved, and the study is not as generizable.
What are parallel interventional studies?
Studies in which groups are randomized, and no switching of intervention groups occurs after that.
What are two types of parallel studies?
simple and factorial
What are cross-over studies?
Studies in which groups serve as their own control by crossing over from one intervention to another during a study. IT allows for a smaller sample size.
What is the washout period?
The period in which subjects return to their baseline health (e.g. the drugs are out of their system).
What is the run in/lead in phase of an interventional study?
Phase in which all study subjects are given one or more placebos for initial therapy (defined time-period) to determine an new baseline of disease.
What are disadvantages of cross over designs?
they are only suitable for long-term conditions, effects may carry over into other groups, complexity in data analysis,
What is the most important endpoint of a study?
the primary outcome. It is the main research question used for developing/conducting a study
What is a composite outcome?
An outcome that combines multiple endpoints into a single outcome. It could be considered a primary outcome.
What are patient-oriented outcomes?
Outcomes that are very significant; they can include death, stroke, hospitalization, etc.
What are surrogate markers?
elements used in place of evaluating patient-oriented endpoints, such as blood pressure for risk of stroke.
What are non-random sample selections/allocations?
Allocation in which subjects do not have an equal probability of being selected or assigned to each intervention group.
What are random sample selections/allocations?
Allocation in which subjects have an equal probability of being assigned to each intervention group.
What is the purpose of randomization?
To make the groups as equal as possible, based on known and unknown important factors (confounders).
What does randomization not guarantee?
equality of groups.
What is is simple randomization?
Randomization in which there is an equal probability for allocation within one of the study grups.
What is blocked randomization?
ensures balance WITHIN each intervention groups (e.g. that they are equal in size).
What is stratified randomization?
ensures balance with known confounding variables (e.g. there is an equal distribution of healthy and sick patients in each group).
What is a single blind masking study?
Study subjects are not informed of the intervention they are receiving, but the clinicians are!
What is a double blind masking study?
Neither clinicians nor patients are informred of the intervention one is receiving.
What is a open-label study design?
everyone knowns which intervention each subject is receiving.
What can post-hoc surveys be used for?
ensuring adequacy of blinding; if the subjects can easily guess which group they are in, the blinding was not successful.
What is a placebo therapy?
a form of blinding in which the placebo treatments are identical to the active treatments. Double dummy is when more than 1 placebo is used.
What is the placebo-effect?
Patients may think they are better due to the type of care they are receiving or the way they are asked questions.
What is the hawthorne effect?
Patients report positive results in placebo because they desire the study to have successful results.
What is post-hoc sub-group analysis?
When researchers compare groups in multiple ways in order to find some sort of correlation; it can be misleading and increases risk of type II errors.
How are drop-outs or lost to follow-ups managed?
they are either included or not included in the study.
What is intent-to-treat?
A researcher uses the information from a drop-out in the study, and converts all missed assessments to a null effect.
What are the benefits of intent-to-treat?
it preserves the randomization process, baseline characteristics, group balance, and maintains statistical power.
What is “as treated” management?
group assigments are ignored, and subjects are allowed to switch groups and be in groups they moved to, ended in, or stayed in the most.
What is a disadvantage of per-protocol analysis?
it biases the estiamtes of effect (commonly over-estimates effect).
How do researchers assess adherence (compliance)?
pill counts, bottle counter-tops and drug levels.
How to researchers improve adherence (compliance)?
frequent follow-ups, treatment alarms/notifications, medication facts/dosage containers.
