[2] Class 16-19:Interventional studies Flashcards
1
Q
What form of study allows for causation?
A
Interventional study
2
Q
Type of study in which Researchers intervene and force ppl into groups allocating Tx
A
Interventional study
3
Q
Which process commonly utilized to accomplish forced allocation in interventional studies?
A
Randomization
4
Q
Which study is considered natural?
A
Observational
5
Q
Type of study where researchers observe subject elements occurring that’re selected by the individual
A
Observational
6
Q
What study type is not able to prove causation:
A
Observational
7
Q
Form of researcher forced allocation in observational studies
A
There is no researcher forced group allocation
8
Q
Human study,clinical trial/study,experimental, investigational study generally means
A
interventional study
9
Q
Name the key difference in Interventional vs. observational studies:
A
Investigator selects “interventions” and allocates study subjects to intervention groups
It is more rigorous in ability to show cause-and-effect: IT CAN PROVE
10
Q
Phases of interventional studies:
A
Pre-clinical-Phase 0-phase 4
11
Q
Phase of the study at the lab ‘bench’ or animal investigation
A
Pre-clinical
12
Q
Exploratory investigational new drug
A
Phase 0
13
Q
3 factors to consider when looking at phases of interventional studies:
A
Sample size,
Length of study,
Purpose-of phase
14
Q
Very small
A
Phase 0
15
Q
Pharmacokinetics:
A
ADME
Absorption
Distribution
Metabolism
Excretion
16
Q
Primary purpose is kinetics of the drug:
A
Phase 0
17
Q
small 20-80 N- short duration-few weeks,
Healthy or diseased volunteers
Possible first time use in ppl,
A
Phase 1
18
Q
Primary purpose: side effects
Secondary: does it actually do what it was set out to do [lower BP/BG]
A
Phase 1
19
Q
Investigational New drug
A
Phase 1
20
Q
Does safety remain a purpose after it is the primary purpose in phase 1?
A
Yes, it just is not be the primary purpose
21
Q
Investigational new drug;indication/population
A
Phase 2
22
Q
Medium N-100-300 and medium duration-few weeks to few months;
Commonly utilize patients w/ Dz of interest…begins to assess efficacy in diseased
A
Phase 2
23
Q
Randomization think->
A
Interventional
24
Q
First phase that begins to look at efficacy:
A
Phase 2
25
Which phase is likely to have narrow inclusion criteria?
Phase 2
26
```
Large N 500-3,000
Longer duration:months-yrs
Ppl have dz of interest
Assessing for short-intermediate safety
Broader inclusion criteria-more clinically relevant
```
Phase 3
27
Primary purpose is to assess for efficacy:
Phase 3
28
The concern w/ more restrictions on exclusions:
More restrictions = more specific and less generalizability
29
Post-marketing post-FDA approval phase:
Phase 4
30
What phase is req'd for FDA approval:
Phase 3
31
Larger N -1000s
Long term effects
Dz population
CAN be interventional or observational design
Phase 4
32
Is phase 0-4 sequential and req'd?
No can go in any order but phase 3 must be approved by FDA
33
FDAs medwatch is an example of what phase :
Phase 4
34
Which study is perfect?
NONE
35
Advantages of interventional trials:
Can prove causation
Only design that can be used for FDA approval
36
Disadvantages of Interventional trial:
Cost
Complexity/time
Ethical considerations
Generalizability-External valid.
37
What is the number one disadvantage to interventional trials?
Ethical considerations are the # 1 reasons why they're not completed
38
Loosens inclusion criteria/ controlling of intervention
More real life/more variable
Allows for others to be doctor of study
Pragmatic interventional study
39
An interventional study w/ a single randomization process and no more subsequently
Simple interventional study
40
Interventional study with 2 or more groups that are randomized into 2 or more sub-groups
Factorial interventional study
41
Ex of factorial study
Fish oil vs. placebo->
| Fish oil and niacin vs. placebo and niacin.
42
Types of factorial:
2x2; 2x2x2
43
Can factorial designs be used to test multiple hypotheses/questions at the same time
Yes
44
BEnefits of factorial design
- Improved efficiency for answering clinical questions
| - req larger study population
45
Disadvantages to factorial interventional study
Increased complexity-barrier for recruitment
Increased risk of drop out[d/t complexity]
May restrict generalizability of results
46
Interventional study where groups simultaneously and exclusively managed
No switching of intervention groups after initial randomization
Parallel interventional study
47
All simple and factorial designs can be
Parallel
48
Interventional study that groups serve as their own control by crossing over from one intervention to another during the study
Cross-over
49
This study type allows for a smaller total n population -sample size
Cross-over study
50
Study that self-controls for cofounders b/c same individual is receiving both Tx / interventions
Cross-over
51
This time period is when the person is cleansing drug/Tx from body prior to receiving other drug/Tx
Wash-out period
52
Cross-over study is typically for what type of disease/condition?
Chronic disease- long standing b/c it it wouldn't be helpful to cure then taker another Tx regime.
53
This can be used to assess placebo-effects, hawthorne-effects and compliance before the study begins:
Run-in; lead-in phase
54
All study subjects blindly given placebo(s) for initial therapy [defined time period] to determine a "new" base-line of disease [satndardization]
Test run= complaisance assessment
Washout period p/t study or can wash-out existing Rx
Run-in / lead-in phase
55
Disadvantages for cross-over study designs:
- Only suitable for long-term conditions- not curable [short term relief]
- duration of study for each subject is longer
- carryover effect during washout
- Tx by time period interaction
- complexity in data analysis
- smaller N req'ment applies only sometimes
56
Most important key outcome
It is the main research question/hypothesis for conducting study
Primary outcomes
57
Lesser importance yet still valuable outcome
Possible for future hypothesis generation
Secondary/tertiary/etc. outcome
58
Combines multiple endpoints into a single outcome
Can be considered primary outcome and secondary outcomes can be individual outcome elements
Composite outcome
59
Ex of POEMs (patient oriented endpoints
Death, stroke, MI, hospitalization, preventing need for dialysis
60
Ex of DOEs Disease oriented endpoints
Risk for stroke
Risk for MI
Worsening in renal function
61
Sample selection in which subjects don't have equal probability of being selected or assigned to each intervention group
"First couple of people that happen to walk by"
Non-random sample selection
62
Sample selection in which Subjects do have an equal probability of being assigned to each intervention group
Created by random number generators
Random sample selection(most commonly utilized
63
Random sampling hopefully removes:
Bias
64
What is the purpose to randomization:
To make groups as equal as possible
65
Attempts to reduce systematic diffferences [bias] between groups that could impact results
Based on known and unknown factors [confounders]
Randomization
66
W/ randomization is equality guaranteed?
NO not guaranteed
67
Which table typically shows group characteristics such as possible cofounders and p values:
Table 1
68
Table 1
Documentation of equality of groups [effectiveness of randomization process] reported in 1 of several locales : p values
69
3 types of randomization
Simple
Blocked
Stratified
70
Equal probability for allocation within one of the study groups
Basic randomization- hopeful
Simple randomization
71
Ensures balance within each intervention groups
When researchers want to assure that all groups are equal in size
More hands on approach for researcher-when study req's exact #'s
Blocked randomization
72
Ensures balance w/ known confounding variables
Ex: age, Dz, gender, comorbidities
Can also pre-select levels to be balanced w/in each interfering factor [cofounder]
More hands on approach for researchers
Stratified randomization
73
3 types of masking:
Single-blind
Double-blind
Open-label
74
Masking in which study subjects aren't informed which intervention theyre receiving [but clinician/researchers know]
Single-blind masking
75
Masking in which neither investigators nor study subjects are informed which intervention each subject is receiving
Double-blind masking
76
Masking in which everyone knows which intervention each subject is receiving
Open-label
77
How would you test a IM shot vs. PO tablet
Make each group receives both types of intervention, no matter which route is true Rx to prevent bias
78
What can be used to asses adequacy of blinding?
Post hoc surveys
79
Inert Tx made to look identical in all aspects to active Tx
Placebo / dummy therapy
80
What is it called if more than 1 placebo / dummy therapy is used
Double-dummy
81
Improvement in conditions by power of suggestion and due to the care provided
Can be as large as 30-50%
Placebo effect
82
Desire of the study subject to "please" investigators by reporting positive results [improvement], regardless of Tx allocation
Desire for positive outcomes
Hawthorne effect
83
Hawthorne effect can make up part of the rate of:
Placebo effect
84
Define post hoc subgroups analysis
A stepwise multiple comparisons procedure used to identify sample means statistically different from each other
85
When is post-hoc sub-group analysis accepted?
It is accepted as appropriate by most when it is prospectively planned for hypothesis generation
86
When is post-hoc sub-group analysis not accepted?
Not accepted as appropriate when its not prospectively planed
87
When post-hoc sub-group analysis is not accepted, what is the term used to define how the stat was found?
'Fishing' or 'data-dredging'
88
Why is fishing or data dredging not a good thing? 2 reasons
Reduces Power
And
Increases risk of type 2 error
89
What should be included in the sample size determination?
Add in for anticipated drop-outs/ lost to F/u
90
3 ways to manage drop-out/lost to f/u rates:
Intention to treat
Per-protocol or efficacy-analysis
As treated
91
Which way of managing drop-outs is most conservative?
Intent(ion)-to-treat
92
2 procedures for intent to treat:
Last known asssessment used for all subsequent, yet MISSED assessments
Convert subsequent missed assessments for a subject to null-effect (no benefit/change)
93
Do authors tell you how they manage drop-out?
Yes, authors must disclose the form of drop-out management they will use
94
Results of intent to treat [3]:
- Preserves randomly selected process
- preserves baseline characteristics and group balance at baseline which controls for known and unknown confounders
- maintains statistical power
95
Technique of ignoring drop-outs
Including only compliant subjects
Per-protocol or efficacy analysis
96
What is the customarily set rate of compliance w/ per protocol or efficacy analysis?
80-90%
97
Technique where drop-outs of study are treated
'As-treated'
98
Technique for managing drop-outs that allows ignoring group assignments-allows subjects to switch groups and be evaluated in group they moved to, end in, or stay in most
'As-treated'
99
Per-protocol dropout management technique results in:
Biases estimates of effect (commonly over-estimates effects)
Reduces generalizability
100
Ways to assess compliance/adherence
Drug levels
Pill counts
Pill bottle counters [lids]
101
Why is adherence used more than compliance now?
Compliance has a negative connotation to it by being forceful.
Adherence allows pt in decision making process...kind of
102
Methods to improve adherence:
Frequent f/u visits [communication]
Tx alarms/ notifications
Rx blister packs or dosage containers
