Human Subject Research:

Principles, Design, & Approach

IKS 592_9
2 credits
June 9 - 18
 A little bit about
me
A m i t S e t hi , P h D , O T R /L
D ir e c to r N E u ra l P la s ti c ity, R e h a bi lit a ti on
& M ov e m e n t D y na m i c s (N E R D ) L a b
D e p a rt m e nt s o f O c cu p a ti o na l & R e c re a t io n al
T h e ra p ie s , B i o m e di c al E n g in e er in g , Ph y s ic a l Th e r ap y
& A th l et ic Tr a in in g
U n i v e rs i ty o f U ta h , S al t La k e C i ty, U S A
Amit’s Background

3
Who is Amit?

4
Why do I need this course?
Course introduction
General expectations
• Be on time
• Attendance in first 5 minutes
• Email me in advance and copy Dr. Arnav Bhavsar if you are
going to miss the class
• Silence your phone
• No eating in class, eat in the break
• Immersive group discussions
• Ask questions during the questions slide
• Course notes – google drive
 Module 1: Rehabilitation
Treatment Specification System
Objective
• Rehabilitation Treatment Specification System for developing
treatment protocols
 Activity
Groups 1-2:
Think of a situation from your experience where you tried every treatment to the
best of your knowledge in your field and still there. Describe the treatment and
identify a couple of reasons of why do you think the client did not show
improvement?

Groups 3-4:
Think of a situation where you provided similar treatments to two clients, one client
improved but the other showed minimal improvement? Describe the treatment and
identify a couple of reasons for the discrepancy in the effect of treatment?
 Problems with IKS treatments
• Lack of standardized ways to:
- define and describe treatments
- less specificity
- effectively communicate the elements of our treatments
with clients and other members of our team
Rehabilitation Treatment Specification System
(RTSS)
How do we develop treatments?

Identify
Assess Treat
problem
Think and write down the steps you take to develop
a treatment plan after identifying the problem

Identify
Assess Treat
problem
How do we develop treatments?

?
Assess Identify ? Treat
problem
QUESTIONS
What are the steps to develop a treatment protocol?
CAUSALITY

Active Mechanism Target

Ingredients (s) of Action

• What the • How the • Aspect of

clinician treatment functioning
does (or is expected directly
selects) to work targeted
for change

TREATMENT SPECIFICATION
 Example of development of treatment
in medicine
Goal: Decrease Headache by taking Crocin

Paracetamol Prostaglandins Headache

Active Ingredient Mechanism of Action Target

QUESTIONS
 Example of development of treatment
in medicine
Goal: Decrease Headache by taking Crocin

Paracetamol Prostaglandins Headache

Active Ingredient Mechanism of Action Target

 Understanding the mechanism
is important to….
- Develop, test and - Explain how the - Identify who
identify the active intervention works responds to the
ingredients of an - Refine intervention intervention
intervention parameters

WHAT HOW WHO

Aickin (2007); Dijkers et al.

(2014)
QUESTIONS
What: Develop, test and validate the
theoretical basis of an intervention
 Mechanistic studies help to identify the
active ingredient(s) of an intervention

Intervention
Active ingredients

Problem Goal
Dijkers et al. (2014)
Intervention:
Strength-training

Problem: Goal: Heavy-

muscle weakness weight lifting
 Active
ingredient:
Weight-lifting

Problem: Goal: Heavy-

muscle weakness weight lifting
QUESTIONS
Behavioral interventions are complex

• Often there are:

- more than 1 active ingredients
- more than 1 mechanism of action
- more than 1 target
 My research: Improve hand function
after stroke
Intervention: combined
brain and hand stimulation

Overall Problem:
hand function Goal: use of weak
hand in daily tasks
The overall decreased hand function problem
is further divided into three sub-problems
Intervention: combined
brain and hand stimulation

Overall Problem:
hand function

brain sensori- hand learned Goal: use of weak

motor activity weakness non-use hand in daily tasks
 Intervention: combined brain and
hand stimulation
Non-Invasive Brain Stimulation
(NIBS)

Repeated task practice with

Functional Electrical Stimulation
(FES)
Video of intervention
 There are three main active ingredients in the
combined brain and hand stimulation intervention

Intervention: combined
brain and hand stimulation
Active
ingredients

NIBS FES Repeated task practice

Problems

brain sensori- hand learned Goal: use of weak

motor activity weakness non-use hand in daily tasks
QUESTIONS
Understanding the problem helps to develop
‘what’ type of active ingredients constitute
the intervention
How: Explain how an intervention works
: Refine intervention parameters
Active ingredient produces the desired goal
via a mediator
Intervention Mediator: variable
which causes the
Active ingredient
change in the goal

Mediator
(or change agent)

Problem Goal
Baron et al., (1986); Dijkers et al., (2014)
 We need to measure the mediator and the goal
to understand ‘how’ active ingredients work

Intervention Measure
Active ingredient
Mediator
(or change agent)

Problem Goal

Measure
 Muscle strength
Intervention:
Strength-training

Mediator:
Muscle strength

Problem: Goal: Heavy-

muscle weakness weight lifting
Weight-lifting
performance
QUESTIONS
 NIBS mediates hand function by increasing the
activity of sensori-motor brain waves
Intervention: combined
brain and hand stimulation

Active NIBS
ingredients
Mediator:
Activity of sensori-
Overall Problem motor brain waves
hand function

brain sensori- Goal: hand use

motor activity
 NIBS mediates hand function by increasing the
activity of sensori-motor brain waves
Intervention: combined
brain and hand stimulation
mu ERD (EEG)
Active NIBS
ingredients
Mediator:
Activity of sensori-
Overall Problem motor brain waves
hand function

brain sensori- Goal: hand use

motor activity
Action Research
Arm Test
 There is an association between the change in
the activity of sensorimotor brain waves and
movement after intervention
Activity of brain waves

Action research arm

(mu ERD %)

test score
Pre Mid Post Pre Post
Increased activity of sensorimotor brain waves
after treatment explains ‘how’ NIBS works
QUESTIONS
 Mechanistic studies can help to refine
intervention parameters

- Target site
- Timing
- Dosage
- Intensity
- Frequency
 A change in the mediation measure without a
meaningful change in the behavioral measure may
suggest increasing the dose of the intervention

(Mechanistic measure)
(Behavioral measure)

Mediator
Goal

Δ ≠ meaningful

Pre Post Pre Post

QUESTIONS
Who: Identify who responds to the
intervention
 Moderators influence the effect
of intervention
Intervention Moderator: qualitative
Active ingredient or quantitative variable
that affects the goal

Goal

Problem Moderator

Baron et al., (1986); Dijkers et al., (2014) Goal

 Individuals may respond differently to
similar treatments
Participant 1: severe Participant 2: moderate
stroke (FM = 20), age = 69 stroke (FM = 38), age = 43

Δ = meaningful
Action research arm

Action research arm

Δ ≠ meaningful
test score

test score
Pre Post Pre Post
 The underlying mediator (mu ERD) shows
differences in response to treatment
Participant 1: severe stroke Participant 2: severe stroke
(FM = 20), age = 69 (FM = 22), age = 43
Activity of brain waves

Activity of brain waves

(mu ERD %)
(mu ERD %)

Pre Mid Post Pre Mid Post

 Stroke severity and age (moderators) influence
the effect of intervention
Intervention: combined brain
and hand stimulation
Active NIBS
ingredient

Goal: hand use

Problems: Moderators:
hand function Severity & Age
Goal:≠ hand use
Stroke severity and age (moderators) may
explain ‘who’ responds to the intervention
QUESTIONS