Chapter 12 (Experimental Studies)
intervention is more effective than a current therapy at curing a disease, or the new intervention is more effective than a placebo at preventing new disease from occurring
"better"
Treatment assigned analysis is better at measuring ________ ________ effectiveness.
real world
can be used to graphically examine the accuracy of a screening or diagnostic test by plotting the false positive rate (x axis) versus the true positive rate (y axis) for the different possible cutoff points of the test
receiver operating characteristics curve/ROC curve
percentage of individuals who are correctly classified by a test as true positives or true negatives
diagnostic accuracy
Key statistical measure:
efficacy
proportion of people who actually have a disease who incorrectly test negative using the new test
false negative rate
Sensitivity and specificity have a(n) ___________ relationship.
indirect
bias in epidemiological study that arises due to systematic measurement error
information bias
strategic action intended to improve individual and/or population health status
intervention
probability ratios used to evaluate the accuracy of screening and diagnostic tests
likelihood ratio tests
experimental study that assigns participants to an intervention or control group using a non random method
quasi experimental design
assignment of participants to an exposure group in an experimental study using a change based method that minimizes several types of possible bias
randomization
when patients receive no treatment
washout period
An ideal screening or diagnostic test would have _______ values for sensitivity, specificity, PPV, and NPV.
100%
negative outcome that may be direct result of study related exposure or may be a coincidental occurrence that is not directly related to the study but happens after an individual receives a study related exposure
adverse event
negative side effect of medication, vaccination, or other exposure, or another bad outcome related to a study
adverse reaction
might occur as result of non random assignment of participants to experimental study groups, such as when people with different exposure histories are not equally distributed across treatment arms
allocation bias
aggregate measure of how well a screening or diagnostic test performs across various cutoff points
area under the curve (AUC)
treatment and nontreatment groups of an experimental study
arms
When to use this approach:
assessing causality
non randomized experimental study that measures the same individuals before and after an intervention so that each participant's before status can serve as that individual's control
before and after study
experimental design elements that keeps participants (sometimes members of research team) from knowing whether a participant is in the active intervention group or the control group
blinding
allocation method that randomly assigns some groups of people to an intervention group and other groups of people to a control group; randomization occurs at the group rather than individual level
block randomization
residual effects from the first part of an experimental study that may bias the results of the second part of a crossover study if a sufficient washout period between the two arms of the study are not implemented
carryover effect
Objective:
compare outcomes in participants assigned to an intervention or control group
source population is appropriate and the research study does not exploit individuals from populations that are unlikely to have continued access to the therapy if it is found to be successful
distributive justice
Primary study question:
does the exposure cause the outcome?
In an experimental trial, the exact _____, _______, and ___________ of the exposure are known.
dose, duration, and frequency
neither participants nor the people assessing the participants' health status know which participants are in an active group or a control group
double blind
calculated with the same equation as efficacy, but refers to results obtained under real world, less than ideal conditions
effectiveness
measure of success of an intervention that is calculated as the proportion of individuals in the control group who experienced an unfavorable outcome but could have expected to have a favorable outcome if they had been assigned to the active group instead of the control group
efficacy
evaluation of the cost effectiveness of an intervention that is based on both its effectiveness and resource considerations
efficiency
experimental research should be conducted only when there is genuine uncertainty about which treatment will work better
equipoise
aims to demonstrate that a new intervention is as good as some type of comparison
equivalence trial
Requirement:
experiment is ethically justifiable
tests several different interventions in a various combinations within one trial
factorial design
proportion of people who actually do not have a disease who incorrectly test positive using the new test
false positive rate
Experimental studies are the ______ _________ for assessing causailty
gold standard
reference test shows the actual presence of disease in affected people
gold standard
A larger LR+ (> 10) indicates a ______ test.
good
A smaller LR- (< 0.1) indicates a ______ test.
good
_______ efficacy is an indication that an intervention is successful
high
AUC values can range from 0 to 1, 0 indicating a test that is ______ 100% of the time and 1 indicating a test is ________ 100% of the time.
incorrect; correct
Adverse events that occur during a research study must be immediately reported to the appropriate ____________ _________ _______.
institutional review board
First step in experimental study is to carefully define the _____________ that participants assigned to the active intervention group will receive and to decide on the __________, ___________, and ______ criteria for the study.
intervention; person, place, and time
experimental design elements that keeps participants (sometimes members of research team) from knowing whether a participant is in the active intervention group or the control group
masking
research study in which the independent variable is not manipulated by the researcher but instead changes due to external forces
natural experiment
inactive comparison that is similar to the therapy being tested
placebo
set of principles and procedures defined by governments or other groups to guide decision making and resource allocation
policy
statistic that examines whether a diagnostic test is good at predicting the presence of disease
positive likelihood ratio (LR+) test
proportion of people who test positive with the new test who actually have the disease
positive predictive value (PPV)
test used for comparison when examining the validity of a new diagnostic test
reference standard
information bias that occurs when members of one study group systematically underreport an exposure or outcome
reporting bias
type of secondary prevention in which all members of a well defined group of people are encouraged to be tested for a disease based on evidence that members of the population are at risk for the disease and early intervention improves health outcomes
screening
proportion of people who actually have a disease who test positive using the new test
sensitivity/true positive rate
Population:
similar participants are randomly assigned to an intervention or control group
use of a coin toss, a random number generator, or some other simple mechanism to randomly assign each individual in an experimental study to one of the exposure groups
simple randomization
participants do not know whether they are in active group or control group
single blind
includes all participants, even if they were not fully compliant with their assigned protocol
treatment assigned analysis/intention to treat analysis
experimental data includes only the participants who were fully compliant with their assigned intervention or comparison procol
treatment received analysis
An ideal screening or diagnostic test would have a ___ rate of false positive and false negative outcomes.
0%
false positive rate formula:
1 - specificity
Experimental trials are used for what three types of trials?
1) clinical (new therapies) 2) field (vaccines) 3) community (environmental interventions)
First steps:
1) decide on the intervention and eligibility criteria 2) define what will constitute a favorable outcome 3) decide what control is an appropriate comparison for the intervention 4) decide whether binding will be used to prevent participants and/or the researchers who will assess outcomes from knowing whether a participant has been assigned to the intervention or the control group
All experimental study designs require careful descriptions of what 4 things?
1) the intervention 2) type of control and why it's appropriate 3) how participants will be assigned to groups 4) end point that will constitute favorable outcome
The first step description should include what 4 things in an experimental study?
1) what the intervention will be 2) the eligibility criteria for participants 3) where and how participants will receive the intervention 4) when, how often, and for what duration participants will receive the intervention
type of bias that occurs when participants in a study change their behavior for the better because they know they are being observed
Hawthorne effect
Experimental studies sometimes include a control group of participants who are randomly assigned to maintain their routines, but this method is usually not preferred. Why?
Raises ethical concerns about discouraging adoption of healthier lifestyles during the course of the study and the Hawthorne effect
information bias that occurs when a population group that is routinely screened for adverse health conditions incorrectly appears to have a higher than typical rate of disease because more frequent testing enables a higher case detection rate in that population than in the general population
detection bias
experiment in which some of the participants are assigned to an intervention group and some are assigned to a non active comparison group
controlled trial
NNT and NNH are often used for _______ ____________ analysis
cost effectiveness
randomly assigns some participants to receive the active intervention first and then the control, and assigns the other to receive the control first and then the active intervention
cross over design
value that divides a numeric variable into separate categories
cutpoint/threshold
statistic that examines whether a diagnostic test is good at predicting the absence of disease
negative likelihood ratio (LR-) test
proportion of people who test negative who actually do not have the disease
negative predictive value (NPV)
aims to demonstrate that a new intervention is no worse than some type of comparison
non inferiority trial
What to watch out for:
noncompliance
number of people who would need to receive a particular treatment in order to expect that one of those people would have a particular adverse outcome
number needed to harm (NNH)
expected number of people who would have to receive a treatment to prevent an unfavorable outcome in one of those people
number needed to treat (NNT)
information bias that occurs when an observer intentionally or unintentionally evaluate participants differently based on their group membership
observer bias
Most quasi experimental studies use both ____ and _____ __________ tests to compare the two arms of a controlled study
pre and post intervention
scientific study of which preventive health interventions are effective in various populations, how successful the interventions are, and how well they can be scaled up for widespread implementation
prevention science
all participants volunteer for study without being unduly influenced by the prospect of being compensated and participants understand what research entails
principle of respect
balance likely benefits and risks
principles of beneficence and nonmaleficence
experimental study in which some participants are randomly assigned to an active intervention group, the remaining participants are assigned to a control group, and all participants from both groups are followed forward in time to see who has a favorable outcome and who does not
randomized controlled trial (RCT)
test that can detect the presence of a pathogen in a small drop of blood (or other bodily fluid) within 15 to 30 minutes
rapid diagnostic test (RDT)
proportion of people who do not have the disease who test negative with the new test
specificity/true negative rate
existing therapy that is used as a comparison for a new therapy being experimentally tested
standard of care
division of a population into subgroups prior to randomly but systematically assigning each individual within each subgroup to one of the exposure groups in an experimental study
stratified randomization
aims to demonstrate that a new intervention is better than some type of comparison, not merely as good as the comparison
superiority trial
information bias that occurs when a population group that is routinely screened for adverse health conditions incorrectly appears to have a higher than typical rate of disease because more frequent testing enables a higher case detection rate in that population than in the general population
surveillance bias