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