Chapter 14 principles of clinical trials

Question 1

Clinical trial

Answer 1

Designed to test hypotheses about comparative effects

Question 2

Types of clinical trials

Answer 2

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

Question 3

Therapeutic trials

Answer 3

Examine the effect of a treatment or intervention on a particular disease or condition

Question 4

Diagnostic trials

Answer 4

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

Question 5

Preventive trial

Answer 5

Evaluates whether a procedure or agent reduces the risk of developing a disease

Question 6

The Gold standard for experimental research iiiiiis….

Answer 6

The randomized controlled trial (RCT)

Question 7

Randomized controlled trial

Answer 7

Structure provides a rigorous balance to establish CAUSE and EFFECT relationships

Question 8

What type of trial is considered the highest form of evidence to support an intervention?

Answer 8

RCT

Question 9

The basic structure of an RCT

Answer 9

Includes 2 groups, each getting a difference treatment condition, with measurements taken before and after intervention to compare outcomes

Question 10

Treatment arms of study

Answer 10

Experimental group and control groups

Question 11

An RCT qualifies as a true experiment because of the 3 requisite design characteristics: _______ _______ _______

Answer 11

Manipulation of variables
Random assignment
Use of a control group

Question 12

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?

Answer 12

Independent Variable

Question 13

Two types of independent variables

Answer 13

Active variable and attribute variable

Question 14

Active variable

Answer 14

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

Question 15

Attribute variable

Answer 15

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.

Question 16

When the only effect of one or more attribute variables is studied, the research cannot be considered a true experiment, T/F?

Answer 16

T
Need an active variable which can be manipulated by the experimenter
Attribute variables are like age, gender diagnosis

Question 17

Random assignment

Answer 17

Means that each subject has an equal change of being assigned to any group

Question 18

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

Answer 18

T

Question 19

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

Answer 19

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

Question 20

Types of random assigment

Answer 20

Simple, block, stratified, cluster, random consent design, assignment by patient preference, run in period

Question 21

Simple random assignment

Answer 21

Each member of the population has an equal chance of being chosen. Subjects are assigned to groups using a form of randomization

Question 22

Block random assignemtn

Answer 22

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

Question 23

Stratified random assignemtn

Answer 23

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

Question 24

Cluster random assignment

Answer 24

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

Question 25

Random consent design

Answer 25

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

Question 26

Assignment by patient preference

Answer 26

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

Question 27

Run in period

Answer 27

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.

Question 28

Allocation concealment

Answer 28

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

Question 29

Control groups

Answer 29

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

Question 30

Attention control group

Answer 30

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.

Question 31

Wait list control group

Answer 31

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.

Question 32

Active controls

Answer 32

Conventional methods of care or established standards of practice

Question 33

Blinding

Answer 33

Assuring that those involved in study are unaware of a subjects group assignment

Question 34

Double blinding

Answer 34

Where the investigators nor the subjects know the identity of treatment groups until after data are collected

Question 35

Sometimes, only single blinding is possible, t/f

Answer 35

T
For many active rehab / surgical procedures, double blind study difficult

Question 36

Unmasking or breaking the blind code

Answer 36

When an adverse reaction event has occurred for a single patient - obligated to break the blind code

Question 37

Open label trial

Answer 37

Open trial, both researches and subjects know which treatment is being administered - can create bias

Question 38

Detection bias/ascertainment bias

Answer 38

Can create a systematic difference in how outcomes are measured when assessors know group assignment

Question 39

Performance bias

Answer 39

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

Question 40

RCT have 2 important restrictions in their design.

Answer 40

1. Strict and often broad specifications of exclusion criteria for subjects
2. Specification of a standardized protocol so that the intervention and control conditions are administered in the same way to all participants within each group

Question 41

PCT

Answer 41

Pragmatic clinical trials

Question 42

Pragmatic clinical trials / practical clinical trials key points

Answer 42

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

Question 43

PCTS allow for more direct application to clinical practice with stronger generalization , T/F

Answer 43

T

Question 44

Preclinical phase

Answer 44

Testing on animals

Question 45

Phase 1 of trial

Answer 45

Testing on small healthy groups to understand side effect etc, 20 people groups

Question 46

Phase 2 trial

Answer 46

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

Question 47

Phase 2 a
Phase 2 b

Answer 47

Phase 2 a to study dosage
Phase 2 b to study efficacy

Question 48

Phase 3 trial

Answer 48

RCT with thousands of patients

Question 49

Phase 4 trials
Phase IV trials

Answer 49

After a intervention has been improved, what else do we need to know trials

Question 50

Superiority trials

Answer 50

One treatment better than the other test

Question 51

Non inferiority trials

Answer 51

When goal of a trial is to show that a new treatment is as good as standard care

Question 52

Equivalence trials

Answer 52

Focused on showing that new treatment is no better and no worse than the standard therapy .