Chapter 14 principles of clinical trials Flashcards
Clinical trial
Designed to test hypotheses about comparative effects
Types of clinical trials
Therapeutic trials - look at effect of a treatment
Diagnostic trials - how accurate are tests we use for disease states
Preventive trial - does the procedure/agent reduce the risk of developing a disease
Therapeutic trials
Examine the effect of a treatment or intervention on a particular disease or condition
Diagnostic trials
Help to establish the accuracy of tests to identify disease states. Usually uses observational studies, these trials can establish a tests clinical importance and its relative efficacy and efficiency against similar tests
Preventive trial
Evaluates whether a procedure or agent reduces the risk of developing a disease
The Gold standard for experimental research iiiiiis….
The randomized controlled trial (RCT)
Randomized controlled trial
Structure provides a rigorous balance to establish CAUSE and EFFECT relationships
What type of trial is considered the highest form of evidence to support an intervention?
RCT
The basic structure of an RCT
Includes 2 groups, each getting a difference treatment condition, with measurements taken before and after intervention to compare outcomes
Treatment arms of study
Experimental group and control groups
An RCT qualifies as a true experiment because of the 3 requisite design characteristics: _______ _______ _______
Manipulation of variables
Random assignment
Use of a control group
A group in a study may get the experimental intervention and the other group may get the control condition. The experimental intervention and the control condition can be considered what part of the study?
Independent Variable
Two types of independent variables
Active variable and attribute variable
Active variable
One that is manipulated by the experimenter so that subjects are assigned to levels of the independent variable
I.e., in a cardiac study, patients were assigned to receive the exercise/education program or usual care. Therefore, treatment was an active variable
Attribute variable
A factor that cannot be assigned because it is an inherent characteristic of the participants, such as age gender diagnosis - CANNOT be manipulated by the experimenter.
When the only effect of one or more attribute variables is studied, the research cannot be considered a true experiment, T/F?
T
Need an active variable which can be manipulated by the experimenter
Attribute variables are like age, gender diagnosis
Random assignment
Means that each subject has an equal change of being assigned to any group
If we can assume that groups are equivalent at the start of the experiment, then we can have confidence that differences observed at the end of the study are due to the experimental intervention and no other confounding factors, T/F
T
When random assignment does not successfully balance the distribution of intersubject differences, there are several design and statistical strategies that can be used, like ch 15 is about - design validity
When random assignment does not successfully balance the distribution of intersubject differences, there are several design and statistical strategies that can be used, like ch 15 is about - design validity
Types of random assigment
Simple, block, stratified, cluster, random consent design, assignment by patient preference, run in period
Simple random assignment
Each member of the population has an equal chance of being chosen. Subjects are assigned to groups using a form of randomization
Block random assignemtn
Subjects are randomly divided into even numbered subgroups, called blocks. Within each block, subjects are randomly assigned to treatment arms. This assures an equal number of subjects within each treatment group
Stratified random assignemtn
Members of the population are grouped by a relevant characteristic in different strata. Members within each stratum are then randomly assigned to groups, assuring that each group has a similar number of subjects from each stratum
Cluster random assignment
Clusters of subjects are identified, typically by site. Each site is randomly assigned to a treatment group and all individuals at that site get the same treatment
Random consent design
Potential subjects are assigned randomly to groups before seeking consent to participate. Only those assigned to the experimental group are approached for consent. Those assigned to standard care do not supply consent. Outcomes for both groups are compared
Assignment by patient preference
Subjects are given a choice of exp interventions. Those who express no preference are randomly assigned to either group and their results examined. Those who express a preference are assigned to that treatment and their results are analyzed separately
Run in period
As a way of assuring compliance, all subjects are given a placebo during a run in period. They are monitored to determine adherence to the protocol. Only those who comply are then randomized to be part of the study.
Allocation concealment
Ensuring that group assignment is done without the knowledge of those involved in the experimental process, thereby providing another assurance that bias is not involved in group formation
Control groups
This group may receive a placebo or sham treatment, a standard treated ent that will act as a basis of comparison for a new treatment
Attention control group
Like for an exercise program, this provides some type of social or educational activity for the control group, to rule out the possible impact of the exercises groups interaction or the attention that a treatment group would receive.
Wait list control group
The experimental treatment is delayed for the control subjects. The control group may be asked to stop any activities that would mimic the treatment and are measured as control subjects during the first part of the treatment. They are then scheduled to receive the treatment following completion of study. This has appeal when it is considered unethical to deny treatment, as long as the delay is not of unreasonable length.
Active controls
Conventional methods of care or established standards of practice
Blinding
Assuring that those involved in study are unaware of a subjects group assignment
Double blinding
Where the investigators nor the subjects know the identity of treatment groups until after data are collected
Sometimes, only single blinding is possible, t/f
T
For many active rehab / surgical procedures, double blind study difficult
Unmasking or breaking the blind code
When an adverse reaction event has occurred for a single patient - obligated to break the blind code
Open label trial
Open trial, both researches and subjects know which treatment is being administered - can create bias
Detection bias/ascertainment bias
Can create a systematic difference in how outcomes are measured when assessors know group assignment
Performance bias
Occurs when there is a difference in the care that is provided or exposure to other factors outside the actual intervention, which can influence participants behavior
RCT have 2 important restrictions in their design.
- Strict and often broad specifications of exclusion criteria for subjects
- Specification of a standardized protocol so that the intervention and control conditions are administered in the same way to all participants within each group
PCT
Pragmatic clinical trials
Pragmatic clinical trials / practical clinical trials key points
Incorporates a diverse patient pop with min exclusion
Participants are recruited directly from various practice settings
Controls are active, often based on usual care or other commonly used interventions
Treatment proceeds as it would in typical clinical situations
Data collection focuses on important clinical outcomes such as patient satisfaction, quality of life, mobility and function
PCTS allow for more direct application to clinical practice with stronger generalization , T/F
T
Preclinical phase
Testing on animals
Phase 1 of trial
Testing on small healthy groups to understand side effect etc, 20 people groups
Phase 2 trial
After being shown safe in humans, time to explore its efficacy by measuring relevant outcomes - 100 to 300 people in groups, these trials may take several years
Phase 2 a
Phase 2 b
Phase 2 a to study dosage
Phase 2 b to study efficacy
Phase 3 trial
RCT with thousands of patients
Phase 4 trials
Phase IV trials
After a intervention has been improved, what else do we need to know trials
Superiority trials
One treatment better than the other test
Non inferiority trials
When goal of a trial is to show that a new treatment is as good as standard care
Equivalence trials
Focused on showing that new treatment is no better and no worse than the standard therapy .
