Research Methodology

in Rehabilitation
Research methodology
& Biostatistics
Study designs
EXPERIMENTAL STUDY DESIGNS
Experimental design
An experiment is theoretically able to exert control over most threats to internal validity,
providing the strongest evidence for causal relationships.

The randomized controlled trial (RCT) is considered the gold standard of true experimental
designs.

In a true experimental design, subjects are randomly assigned to at least two comparison
groups.
Experimental designs may be differentiated according to how subjects are assigned
to groups.

In completely randomized designs, also referred to as between-subjects designs, subjects are
assigned to independent groups using a randomization procedure.

In a randomized block design subjects are first classified according to an attribute variable (a
blocking variable) and then randomized to treatment groups.

A design in which subjects act as their own control is called a within-subjects design or a
repeated measures design
Quasi-experimental
A quasi-experimental design does not meet the requirements of a true experiment, lacking
random assignment or comparison groups, or both.

Even though quasi-experimental designs cannot rule out threats to internal validity with the
same confidence as experimental designs, many such designs are appropriate when stronger
designs are not feasible.

Quasi-experimental designs represent an important contribution to clinical research, because

they accommodate for the limitations of natural settings, where scheduling treatment
conditions and random assignment are often difficult, impractical or unethical.
SELECTING A DESIGN
When an experimental design is deemed appropriate, the choice of a specific
design will depend on the answers to six critical questions about how the study
is conceptualized:
1. How many independent variables are being tested?
2. How many levels does each independent variable have, and are these levels
experimental or control conditions?
3. How many groups of subjects are being tested?
4. How will subjects be assigned to groups?
5. How often will observations of responses be made?
6. What is the temporal sequence of interventions and measurements?
 DESIGNS FOR INDEPENDENT
GROUPS
SINGLE-FACTOR DESIGNS FOR INDEPENDENT GROUPS
Pretest-Posttest Control Group Design
A single-factor design, also called a one-way design, is used to structure the investigation
of one independent variable. The study may include one or more dependent variables.
The pretest-posttest control group design is the basic structure of a randomized
controlled trial. It is used to compare two or more groups that are formed by random
assignment. One group receives the experimental variable and the other acts as a control. These
independent, groups are also called treatment arms of the study. Both groups are tested prior to
and following treatment.

This design is considered the scientific standard in clinical research for establishing a cause-and-
effect relationship.
Two-group pretest-posttest design
Multi-group pretest-posttest control
group design
Analysis of Pretest-Posttest Designs.
Pretest-posttest designs are often analyzed using change scores, which represent the difference
between the posttest and pretest.

With interval-ratio data, difference scores are usually compared using an unpaired
t-test (with two groups or a one-way analysis of variance (with three or more groups).

With ordinal data, the Mann-Whitney U-test can be used to compare two groups, and
the Kruskal-Wallis analysis of variance by ranks is used to compare three or more
groups.
Posttest-Only Control Group Design
Analysis of Posttest-Only Designs
With two groups, an unpaired t-test is used
with interval-ratio data, and a Mann-Whitney U-test with ordinal data.
With more than two groups, a one-way analysis of variance or the Kruskal-Wallis analysis of
variance by ranks should be used to compare posttest scores.
Study designs
Multi-Factor Designs for Independent
Groups
Factorial Design: A factorial design incorporates two or more independent variables,
with independent groups of subjects randomly assigned to various combinations of levels of the
two variables.
Two-Way Factorial Design.
A two-way factorial design incorporates two independent variables, A and B.
This design allows us to ask three questions of the data:
(1) Is there a differential effect of moderate versus vigorous exercise?
(2) Is there a differential effect of exercising at home or a community center?
(3) What is the interaction between intensity and location of exercise?
The answers to the first two questions are obtained by examining
the main effect of each independent variable, with scores collapsed
across the second independent variable.
The third question addresses the interaction effect between the two independent
variables. This question represents the essential difference between single-factor and
multifactor experiments.

Interaction occurs when the effect of one variable varies at different levels of the second
variable.

For example, we might find that moderate exercise intensity is more effective in changing
exercise behavior, but only when performed at a community center.
Three-Way Factorial Design
Then we can examine three double interactions: intensity x location, intensity x frequency, and
location x frequency. For example, the interaction between intensity and location is obtained by
collapsing data across the two levels of frequency of exercise.

Each double interaction represents a two-way design. Finally, we can examine the triple
interaction of intensity, location and frequency. This interaction involves analyzing the
differences among all 8 cells
Analysis of Factorial Designs.
Analysis of Factorial Designs. A two-way or three-way analysis of variance is
most commonly used to examine the main effects and interaction effects of a
factorial design.
Task
Example of 2*2 design

Example of 2*2*2 design

DESIGNS FOR INDEPENDENT
GROUPS
REPEATED MEASURES DESIGNS
Repeated measures design
A repeated measures design, where one group of subjects is tested under all conditions and
each subject acts as his own control.

A repeated measures design can be considered a series of trials, each with a single subject.
Therefore, such a design is also called a within-subjects design, because treatment effects are
associated with differences observed within a subject across treatment conditions, rather than
between subjects across randomized groups.

The major advantage of the repeated measures design is the ability to control for
the potential influence of individual differences.
Single-Factor Designs for Repeated Measures:
One-Way Repeated Measures Des1gn
Cross over
Multi-Factor Designs for Repeated Measures:
Two-Way Design with Two Repeated Measures
Analysis
Analysis of Two-Way Repeated Measures Designs. The two-way analysis of
variance with two repeated measures is used to analyze differences across
main effects and interaction effects.
Mixed Design
A mixed design is created
when a study incorporates
two independent variables,
one repeated across all
subjects, and the other
randomized to independent
groups.
In the comparison of the two exercise programs, subjects were randomly assigned
to treatment groups. Each subject was tested three times (pretest and two posttests).
The variable of exercise program is considered an independent factor because its levels have
been randomly assigned, creating independent groups.
The variable of time is a repeated factor because all subjects are exposed to its three levels.
Therefore, this design is also called a two-way design with one repeated measure, or a 3 x 3
mixed design.
This example illustrates a commonly used approach, where researchers want to establish if the
effects of intervention are long lasting, and not just present immediately following completion
of the program.
Analysis of Mixed Designs
Analysis of Mixed Designs. A two-way analysis of variance with one repeated
measure is used to analyze main effects and interaction effects with a two-way design
with one repeated factor.
SEQUENTIAL CLINICAL TRIALS
Sequential clinical trial is a special approach to the randomized clinical trial,
which allows for continuous analysis of data as they become available, instead of waiting until
the end of the experiment to compare groups.
Results are accumulated as each subject is tested, so that the experiment can be stopped at
any point as soon as the evidence is strong enough to determine a significant difference
between treatments
Measuring Preferences
Preference is defined on the basis of clinically meaningful differences between two
treatments. The specific criteria for expressing preference for one treatment over
another can vary in objectivity.
For instance, if we were measuring the effect of two treatments for increasing range of
motion, we could specify that Treatment A would be preferred if it could produce at
least 20 degrees more of an increase in range than Treatment B. In other words, any difference
between treatments smaller than 20 degrees would not be clinically meaningful, and both
treatments would be considered equally effective.
Any difference greater than 20 degrees would indicate preference, whether that difference was
25 or 100 degrees. If analysis was based on the magnitude of differences, the amount of
difference would be taken into account. The researcher must determine if the magnitude of
difference is important or if the comparison between treatments is adequately assessed simply
by expressing preference.
Example of a Sequential Clinical Trial
Researchers studied the differential effect of low-load prolonged stretch (LLPS) versus
the more traditional high-load brief stretch (HLBS) for treating knee flexion contractures in
elderly patients.21 Subjects were admitted to the study based on the presence of bilateral knee
flexion contractures of at least 3 months' duration, and at least 30 degrees short of full
extension. In addition, subjects had to be unable to walk or pivot transfer without maximal
assistance. Subjects' limbs were randomly assigned to receive either LLPS or HLBS. Treatment
was performed twice daily, 5 days a week, for 4 weeks. Range of motion was measured before
and after 4 weeks, and preference was defined as a difference of at least 10 degrees between
limbs.
 The second type of sequential chart was developed
by Armitage,25 and allows for more flexibility in
design. Different size charts are drawn, allowing for
different expectations of effects. This charts drawn
to detect a significant treatment difference if one
drug regimen was better in at least 85% of the pairs.

 In this format, the boundaries are drawn above and

below a center baseline. Preferences for one
treatment or the other are indicated by moving up or
down from the last plotted point.

 The first four patients favored the 50% dose, the

next three the 25% dose, the next two the 50% dose,
and so on. This example shows an outcome that
moves towards the middle boundary, indicating no
significant difference.
Stopping Rules
After each successive "little experiment" is plotted, the researcher stops to consider the
results of all the pairs completed thus far and makes one of three decisions: (1) Stop and
make a terminal decision to recommend A or B; (2) stop the experiment and make a terminal
decision that treatments A and B are not different; or (3) continue to collect data
because the cumulated data are not yet sufficient to draw a conclusion. This process of
considering cumulative results after each pair of subjects has been tested is called
sequential analysis.
These boundaries represent three stopping rules: (1) If the upper boundary is
crossed, we can make a terminal decision to recommend A; (2) if the lower boundary is
crossed, we can make a terminal decision to recommend B; (3) if the middle boundary
is crossed (either above or below the origin), there is no preference.
Any Question