Interventional study designs Flashcards
What is an intervential study?
research force allocation
(proves causation)
INVESTIGATORS INTERVENES AND A,OCATES STUDY SUBJECTS TO FORCED INTERVENTION GROUPS
Also called clinical trial, clinical study, experimental study, human study, investigational study
what is an observational study?
no research inforced allocation
(may prove causation)
NATURALLY OCCURING
What are the four differenators of intervential studies?
Purpose/focus
Population studies (healthy vs dieased)
Sample Size
Duration
What is the pre clinical phase?
benchmark or animal research
or
before any human involvment is considered
What is phase 0
- single or few doses
does the drug do what it what it theortically mechanically suppose to due
ex: bind to a receptor
2. healthy volunteers
3. very small n
4. very short duration
How is a phase 1 study identified ?
- acess safety/tolerance and pharmokinetics of one or more dosages
- Health and dieased volunteers
- small N (ex 20: 80)
- Short Duraction (few weeks )
Pharmocokinetics is how the body handles the drug
How is phase 2 study identified?
- assess effectiveness (continues to assess safety and tolerability) ; expands on phase 1 purpose
- Dieased volunteers
- may have narrow inclusion criteria for isolation of effects
- Larger N
- (100 to 300)
- Short to medium duration (weeks to months)
may include dose variation
How is a phase 3 study identified?
- assess effectiveness ( PLus dafety adn tolerablility)
- Dieased volunteers
- expansion of inclusion critteria and comparison groups for delineation of effects
- Superiority, noninferiority, equivelancy
- Larger N
- 500 – 3000
- Longer duration few months to a year
THIS IS THE LAST PHASE BEFORE FDA APPROVAL ; may be repeated multple times usually success for 3/5 times
How is phase 4 study indentified ?
- Assess long term safety, effectiveness, and optimal use of risks and benefits
- dieased volunteers
- expand use of criteria (cormobidities/concommited medicatication) for delineated long term safties and effects
- population N
- 100 - 100,000
- Wider duration
- wks to years
What are some ways to idenifty differences in studys?
well…
healthy indivduals only used in phases 0 and 1
efficacy is a focus for phases 3 and 4
Anything on the market already is post FDA approval so thats Phase 4
Phase 3 is used to submitted data about the drug to the FDA
What are thr pros and cons of intervential studies?
- PROs
- Shows causation
- CAuses will prece effects
- only designs used by FDA for approvel process
- Shows causation
- Disadvantages
- cost
- complexity/tmie
- ethical consideration
- generalizability
what is the difference betweent Exploratory and Explanatory (pragmatic studies)?
Exploratory
- answers reseach questrions. Ex When do does strength work
- Proves causation and is very controlled
- Not very repersentative of life
Explanatory (pragmantic Studies)
- Flexability for researchers (more repersentative of life)
- options for switching drugs in and out
- Better description of how to treat diease
- loses precision for controlling
- can let confounders slip in
What is the differene between simple and factorial classifications of a study?
simple = 1 step of randomization into subset groups
Factorial = multiple steps of randomization into different subsets group levels
What benefits does factorial study provdie?
Used to test multiple hypothesis
- Improve efficeiency for answering cinical questions
- Increases study populations sample size (due to increased group #)
- Increases complexity (which may be barrier to rectuitment)
- Increases risk of drop outs ( due to complexity)
- may restrict generalizability of
What is the difference between a parallel interventional study and cross-over?
Parallel
- No switching of interventional groups after initial randomization
- serves as a description of simple and factorial
Cross over
- Groupes serve as their own control by crossing over from one intervention to another during the study
- allows for smaller total N (sample size)
- each patient contributes additional data
What is a wash out and how does it compare with a lead in?
A wash out occurs when your doing a cross over. Before the crossover even starts you have allows physological affects to cease in the subject before he or she can continue with the study
A lead in (run in) is the “wash out peroid” before the study even starts. allows determianation of a new baseline of disease
- USes placebos
- Test subjects and serves as a practice run for the subject
- assensing complience and ect.
what are the disadvantages of cross-over design?
- suittuble for short term relief medication
- not for long term or uncurable conditions
- duration of study for each subject is longer
- carry over effects for each subject is longer
- treatment -by-period- interaction
- different in effects of treatments during a different time peroids
- smaller n if applicable
- complexity in data anaylsis
What are the different types of outcomes/ endpoint of an intervential study?
- Primary
- Most important; key
- Secondary…tertiary….ect..
- lesser importance but valuable
- composite
- multiple endpoints combined into 1
what are examples of patiented oriented endpoints ?
Most clinically revelent
- Death
- Stroke or myocardial infartion
- hospitalization
- peventing need for dialysis
What are examples of dieases oriented endpoints (surrogate markers)
Blood pressure (risk of stroke)
Cholesterol (for risk of heart attack)
Change in SCr (for worsening renal functional)
how does group allocation occur?
Non-random (no equal probability)
and
random (do have equal probabiltiy
What do we randomize?
To make groups as equal as possible based on known and unkown important factoirs (confounders)
Equality of groups is not guarenteed
Documentaation of groups equality as p valules in table, not show in text at key of table or article.
What are the different forms of randomization?
- Simple
- Equal probablity for allocation within one of the study groups
- Blocked
- weighted allocation and ensures balance within in each ainterbention group
- Stratfied
- Wieghted allocation and ensures balance with known confounding variables
What is masking?
- Single blind
- Study subjects are not informed which intervention (treatment ) group they are in
- investigators known
- Double blind
- niether the subjects or the investigaters know what group subjects are in
- Open labeled (unmasked / unblinded)
- study subjects and researchers known what intervention is being recieved
What can be used to assess adequacy of blinding?
Post hoc survey
not accepted as appropriate by most when not prospectively planned
Accepted as appropriate by most when it is prospectively planned or performed for hypotehsis generation and development of future studies
What are different forms of masking?
placebo (Dummy) therapy
- Inert treatments made to look indentical in all aspects to active treatments
- ex: dosage form, dosing frequency, monitoring, therapy requirements
Double dummy = more than 1 placebo
- Placebo effect
- improvement of condition by power of suggestion of being treate (improvement 30% to 50%)
- Hawthorne effect
- Study subjects change their behavior solely due to awareness of being studied or observed
What are ways to manage drops-outs and lost to follow ups
- Including them any way
- intent (ion) to treat -> most conservatice decision
- Ex:
- Last known assessment (observation) used for ( carried forward )
- Converts all subsequent yet missed assessments for a subject to a null effect (no benefit)
- Ignore them
- inlcusion of only compliant or completing subjects
- per protocol or efficacy analysis
- compliance must be predefined customaryly set at 80 to 90%
- Treating them as treated
- as treated
- ignores groups assignments
- allows subjects to switch groups and be evaluated in group they moved to,end in, or stay in most
*
- as treated
What are the impacts of intention to treat and per protocol?
Intention to treat
- Preserves randomization process
- preserves baseline charcteristics and group balance at baseline which controls for known and unkown confounders
- maintains statistical power
per protocol
- biases estimates of effect (commonly over estimates effects )
- reduces generalizabiltiy
What are some methods to of assessing adherence(compliance) and improving it?
Assess
- Drug levels at mutpile sits like hair and blood
- Pilll counts at each visit
- bottle counter tops
Improvement
- frequenct follow up visits / communication
- treatment alarms/ notfications
- medications blister packs or dosage containers
