Interventional Study Flashcards
Factorial interventional study
- 2 or more groups, subdivided into 2 or more groups (more people)
- Randomized more than once
- improve efficacy/Increase complexity
- Increases risk of dropout
- may restrict generalizability off results
- Test Multiple hypothesis
Simple Interventional Study
- Divides groups exclusively into to or more groups
- 1 Randomization process
- Test ONE hypothesis at a time
Parallel Interventional Study
- Groups simultaneously/exclusively Merged
- No switching of groups after initial randomization
- All simple & factorial studies are parallel
Cross-Over interventional study
- Groups serve as their own control by crossing over from one intervention to another (still in the same study)
- Smaller # of people
- comparisons possible between & within groups
Disadvantages of an Interventional Study?
- Cost * Ethical Considerations
* Complexity/time *Generalizability
Advantages of Interventional study?
- The only study with “FDA Approval”
* Cause precedes effect; study has causation
Key Points of an Interventional study?
- clinical: forced to take something experimental
* Randomization
In interventional studies there are 5 phases: describe the pre-clinical phase.
In-lab
In interventional studies there are 5 phases: describe phase 1.
- new drug/device/procedure
- healthy volunteers, first time use in humans
- safety/toxicity
- short duration (weeks)
- usually less than 100 people
In interventional studies there are 5 phases: describe phase 2.
- New drug/device/procedure: in people with the disease.
- increase people: several hundred with a COMMON INTEREST
- toxicity/efficacy
- duration: weeks to months
In interventional studies there are 5 phases: describe phase 3.
- New drug/device/prodecure
- increase people: several thousand w/ disease
- longer duration: Months to years
- Primary Purpose: Efficacy
- superiority vs. non-inferiority
In interventional studies there are 5 phases: describe phase 4.
- post marketing
- long term effects in people with disease
- largest population size
When is a washout study done?
can be done in the middle of a cross over study or at the beginning of any study.
When does the lead-in/Run in take place and what is it used for?
Done at the beginning and allows the researcher to see if the study participants will cooperate with the study rules.
Outcomes/Endpoints of interventional studies
Primary=Most Important
secondary/tertiary/etc= less important but still valuable
Composite= combines multiple endpoints into single outcome
Direct endpoints= Most clinically relevant (ex. death, stroke, MI)
Surrogate Markers= Elements used in place of evaluating direct endpoints (ex. cholesterol, etc)
What does explanatory mean?
it explains the effectiveness of an intervention and only certain people get to play the game.
What does pragmatic mean?
Let everyone with the condition be in the study. More applicable to clinical use.
Disadvantages of cross-over studies
- only suitable for long term conditions
- participation time is longer
- washing-out prolongs study
- complexity of data analysis
- treatment-by-period interaction
Explain sample selection and group allocation
Ex. pts attending morning clinic assigned to 1 group, pts attending afternoon clinic assigned to the other group.
NON-Random: subjects don’t have equal probability of being selected or assigned to each intervention
Random: Subjects do have equal probability of being assigned to each intervention group (most commonly utilized) EX random-number generator
What is the purpose of RANDOMIZATION
- make groups as equal as possible
- attempts to reduce bias
- shown in table 1
- equality of groups NOT guaranteed
- documentation of equality of groups represented as “P” values.
What are the types of Randomization
Blocked: need groups to be equal in number
Stratified: need factor being tested to be equal
- ensures balance with known confounding variables.
Masking: Single Blind
Subjects are not informed which intervention they are receiving.
Masking: Double-Bling
Neither investigator nor subject are informed which intervention each subject receiving
Masking: Open-Label
Everyone knows which intervention they are recieving
Masking: Placebo (dummy therapy)
fake treatment made to look identical to real treatment
Masking: Double-Dummy
more than 1 placebo
Masking: Placebo-effect
improvement of condition by power of suggestion & due to care provided (can be as large as 30-50%)
* subjects want to please investigators
Name the six principles of Bioethics
- autonomy
- beneficence
- Justice
- non-maleficence
- Consent
- Assent
Define Autonomy:
Full/complete understanding of risk and benefits
Define beneficence
to benefit or do good for patients
NON-maleficence
- Do harm
- don’t withhold info
- don’t provide false info
- don’t exhibit professional incompetence
Define consent
agreement to participate based on being fully & completely informed, given by mentally-capable individual of legal consenting age
Define: Assent
agreement to participate based on being fully & completely informed, given by mentally-capable individuals NOT able to give legal consent (children)
What does the Belmont Report provide?
- Respect for persons
- research should be voluntary, autonomous
- Beneficence
- research risk are justified by potential benefits
- Justice
- risk & benefits of the research are equally distributed.
2 Levels or IRB Review
Full Review: ALL interventional trials w/ more than minimal/ no risk to patients. *ALL medication related studies
Exempt: No Patient identifiers, low/no risk, de-identified dataset analysis, environmental studies, use of de-identified existing data/specimens.
What does the Data Safety & Monitoring Board )(DSMB) do?
Review study data as study progresses to asses for undue risk/benefit
Post-Hoc Analysis
Trying o find a pattern you didn’t initially think about at start of study and find statistical test to prove the pattern.
How do you manage drop outs/less-to-follow-ups? List the three types.
- Intent-to-treat
- As-Treated
- Ignore them
Define intent-to-treat
- will keep in study & use what i got
- use most recent assessment for all subsequent assessments
- preserves randomization
- preserves baseline characteristics
- maintains statistical power
Define as-treated
- Ignore group assignments
- allow subjects to switch groups & be evaluated in group they ended/stayed in the most
Define ignore-them group
only tell about subjects who took full dosage.
methods for improving adherence (compliance)
- Frequent follow-up visits/communications
- treatment alarms/notifications
- medication blister packs or dosage containers.
