Lectures 7-9 Flashcards
Population
All individuals making up a common group
What is the study method-selection based on…?
Type of research question (hypothesis) Validity of acquired information Efficiency & practicality Cost/finances Ethics of research question
Sample
A subset or portion of the full population (representatives)
Null Hypothesis
States there is NO (true) difference between the groups being compared
Alternative Hypothesis
States there IS (true) a difference between the groups being compared
Observational Study
Lets nature take its course and we observe outcomes
“natural”
Interventional Study
Investigators select interventions/exposure…force something to be done
“experimental”
T/F: Observational studies can demonstrate causation
False, Interventional studies demonstrate causation
Pre-clinical phase of interventional study
Prior to human investigation (bench/animal research)
Phase 1 of interventional study
New drug/device/procedure
Humans used for first time in short duration (few weeks) to assess safety, toxicity, & pharmacokinetics
Can’t tell long term side-effects
Small number of people (<100)
Phase 2 of interventional study
New drug/device/procedure
Utilize patients with the condition of interest to expand on phase 1 and assess efficacy in diseased population (few weeks to months)
Number of people ~100-300
Phase 3 of interventional study
New drug/device/procedure
Used in patients with condition of interest to determine safety and efficacy for longer duration (months to years)
Number people ~1,000-3,000
Superiority vs. Non-inferiority vs. Equivalency formats
Phase 4 of interventional study
Post-marketing (occurs after product is on the market)
Determine long-term effects in large population of disease patients
Largest number of people
Advantages of Interventional Trials
Shows causation (cause precedes effect) Only design used by FDA for "approval" process
Disadvantages of Interventional Trials
Cost
Complexity/Time
Ethical Considerations
Generalizability (is study population similar to general population and will findings be applicable to them)
Simple Interventional Study Design
Divides subjects into at least 2 groups
Randomized once
Explanatory
Explains effectiveness of intervention
*Problem is that only certain people get to play the game
Pragmatic
Let everyone with the condition be in the study
*More people can play the game, more like real life
Factorial Interventional Study Design
Divides subjects into at least 2 groups and sub-divides each of those groups into at least 2 groups
Randomized more than once
Takes more people
Parallel Interventional Study Design
Groups simultaneously and exclusively managed
No switching groups after initial randomization
(Simple & Factorial study designs are also parallel)
Cross-Over Interventional Study Design
Individuals can cross from one group to another during the study
Wash-Out Period
Time when you “clear” your system to be as drug free as possible when entering a group/study to limit errors/side-effects that aren’t typical
Disadvantages of Cross-Over Design
Only suitable for long-term conditions Longer duration of study Carry-over effects during wash-out Treatment-by-period interaction Complexity in data analysis
Primary Outcome/Endpoint of Interventional Study
Most important/key outcome, main research question
Secondary Outcome/Endpoint of Interventional Study
Lesser importance, yet still valuable
Tertiary Outcome/Endpoint of Interventional Study
Much less importance, but still valuable
Composite Outcome/Endpoint of Interventional Study
Combines multiple endpoints into a single outcome
Direct Endpoints vs. Surrogate Markers
Direct Endpoints: death, stroke, heart attack, preventing need for dialysis, etc.
Surrogate Markers: blood pressure, cholesterol, etc.
Types of sample selection/group allocation for interventional studies
Non-random: Subjects don’t have an equal probability of being selected or assigned to each intervention group
Random: Subjects do have an equal probability of being assigned to each intervention group
Purpose of Randomization
Make groups as equal as possible based on known or unknown important factors
Attempts to reduce bias
Equality NOT guaranteed
T/F: Saying, “There was no significant difference between groups” means the randomization failed.
False, it means the randomization worked
Blocked Randomization
Ensures groups are equal in number
Stratified Randomization
Need factor tested to be in equal numbers in each group
Single-Blind Study
Subjects are not informed to which intervention they are receiving
Double-Blind Study
Neither investigators nor subjects are informed to which intervention the subjects are receiving
Open-Label Study
Everyone knows which intervention each subject is receiving
Post-hoc Survey
Used to assess adequacy of blindness
Blinding should be a 50/50 random mix of correct knowledge of which intervention the subject was receiving
Placebo/Dummy Therapy
Fake treatment made to look just like active treatment
*Double-Dummy: more than 1 placebo
Need 2 placebos if method of ingestion is different for medicines
Placebo-Effect
Improvement of condition by power of suggestion & care provided
*Can be 30-50% increase
Hawthorne-Effect
Desire of subjects to “please” investigators by reporting positive results, regardless of treatment allocation
Run-In/Lead-In Phase
Used to…
Asses protocol compliance
“Wash-out” existing medication
Determine amount of placebo-effect
What are the 4 Principles of Bioethics?
Autonomy: Self-rule/determination, be able to make decisions on their own accord
Beneficence: To benefit or do good for the patient (not society)
Justice: Equal/fair treatment regardless of patient characteristics
Nonmaleficence: Do no harm
Consent
Agreement to participate based on being fully informed and mentally capable/of legal age
Assent
Agreement to participate based on being fully informed and mentally capable NOT of legal age (children)
What did the Belmont Report contain?
3 guiding principles
1) Respect for persons: research should be voluntary/autonomous
2) Beneficence: risks are justified by potential benefits
3) Justice: risks and benefits are equally distributed
Who determines ethical conduct?
Institutional Review Board (IRB): role is to protect human subjects from undue risk
Equipoise
Genuine confidence that an intervention may be worthwhile in order to use it in humans
What agency “puts teeth” behind IRB?
Office of Human Research Protections: administers and enforces regulations
3 levels of IRB review are?
Full Board: used for all interventional trials with more than minimal patient risk (medication related studies)
Expedited: used with minimal risk and no patient identifiers
Exempt: low/no risk, no patient identifiers, environmental studies
What does the Data Safety & Monitoring Board (DSMB) do?
In charge of reviewing study data as study progresses to assess for undue risk or benefit
Assessing adherence (compliance) of interventional studies
Drug levels
Pill counts
Bottle counter-tops
Methods of improving adherence (compliance)
Frequent follow-up visits/communication
Treatment alarms/notifications
Medication blister packs or dosage containers
What are the 3 ways of managing drop-outs?
1) Include them anyway
2) Ignore them
3) Treat them as “treated”
Explain the “include them anyway” method
Use what information you have gathered and keep their statistics in the study either by using last assessment for all future assessments or by converting all past and future assessments to base-line recording
Explain “ignore them” method
Only report data for subjects who took the complete dosage, leave out any drop-outs
