Transcript Pharmacologic Treatment of Cognitive & Behavioral

MODELS OF REHABILITATION
RESEARCH
John Whyte, MD, PhD
Moss Rehabilitation Research Institute
&
Thomas Jefferson University
The ICF & Related Models
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Body structure (disease)
Body function (impairment)
Activity (disability)
Participation (handicap)
Biomedical Research
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Deals primarily with body structure & function
Assumes that functional ability is directly
related to resolution of body structure/
function abnormalities
What about…..
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Improvement in function w/o improvement in
pathology?
Improvement in pathology w/o improvement in
function?
Participation
Body Function
Employment
Sustained
Attention
Parenting
Driving
Public
Speaking
Working
Memory
Language
Comprehension
Diffuse
Axonal
Injury
Contusion
Balance
Motor
Coordination
SensoriDiabetic
neural
Neuropathy
Hearing Loss
Levels of Intervention
LEVEL OF OUTCOME
LEVEL OF
TREATMENT
Body
Structure
Body
Structure
Body
Function
Activity
Participation
Body
Function
Activity Participation
Implications for Research
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Ideally, research should clarify the causal
links among levels in the
enablement/disablement process
Most NIH-funded rehabilitation research to
date stays primarily at one level (and mostly
at body structure/function levels)
Distinction between enablement/ disablement
research and rehabilitation research
2 Case Examples
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The effects of oral antispasticity
medications (Whyte & Robinson, 1990)
The effects of cognitive remediation
(Carney, et al, 1999; Cicerone, et al,
2000)
Implications for Training
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Investigators will need to work in
interdisciplinary teams
Having in-depth knowledge regarding a level
above or below the “target” level can be ideal
Researchers need to build quantitative and
testable models of these interrelationships
Who mentors the linkages?
Using Theory In Rehabilitation
Research
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Is there an overarching theoretical
framework for rehabilitation?
What focused theories are useful for
focused domains?
How can these theories be applied
specifically to treatment research?
Key Elements in Efficacy Study
Design
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Defining the
Defining the
treatment
Defining the
Determining
appropriate study sample
“active ingredients” of
study outcomes
the overall study design
What do we mean by
“treatment theory”?
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A proposed specification of the “active
ingredients” of treatment
A proposed specification of the
mechanism of action of those active
ingredients
Why do we need a treatment
theory?
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Many rehabilitation treatment interventions
are multifaceted and interactive – what
elements or processes make a difference?
Candidate active ingredients are infinite;
we need to constrain them for study
Results of theoretically-driven treatment
studies not only provide an empirical
result; they support theory development
and refinement
Multifaceted Treatments
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May consist of a set of tasks and
activities delivered by specific disciplines
in a particular dose or schedule and
according to a particular protocol
Which of these are important
determinants of treatment outcome?
Reducing the Infinite
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Given multifactorial treatments, how do we
select which aspects to “manualize” in
defining the treatment of interest? The color
of the walls? The gender of the therapist?
Theory, rightly or wrongly, points to the
indispensable, defining aspects of the
treatment
We always have at least covert theories
Theory Development
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An empirical comparison of 2 treatments simply
establishes that one is better than the other; it
provides no guidance how the better treatment
could be improved upon, or what components of
it could be sacrificed without losing potency.
A theory-based comparison eliminates a whole
family of unsuccessful treatments and provides a
dimension along which the better treatment can
be tuned (e.g., reaching training in motorlesioned monkeys)
Treatment Theory Can Inform
Other Aspects of Study Design
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Selection of appropriate study
participants
Selection of appropriate outcome
measures
Selection of the optimal experimental
design
Study Participants
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Given the proposed mechanism of
action, who can realistically benefit?
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Ability to understand and participate in the
critical aspects of treatment (e.g., learn to
use an assistive device)
Requirement for preserved cognitive or
motor capacities (e.g., ability to dorsiflex on
command)
Requirement for social support (e.g., if
treatment primarily targets family support
skills, employer acceptance)
Study Participants (cont.)
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Choose participants that vary in the the
hypothesized “treatment responsive”
characteristics to clarify the mechanism?
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individuals with and without declarative memory
deficits in a study of errorless learning
Individuals with different degrees of social support
in a study of telephone care management
Characterizing the Participants
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Once selected, one must ask whether
the participants in different treatment
groups are “comparable” – comparable
in what way(s)?
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Balance achieved between randomized
groups
Statistical adjustment of differences in
observational studies
Need prior data on prognostic factors
Comparability & Adjustment
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Comparability and adjustment in terms
of prognosis on the outcome measures
chosen (will discuss later)
Comparability and adjustment in terms
of the characteristics that predict
responsiveness to the treatment under
study
Outcome Measures
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Given the proposed mechanism of action
of the treatment, where would you
expect to see treatment impact?
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The most “proximal” impact (as evidence for
the proposed mechanism)
A more “distal” impact (as evidence that the
change achieved has clinical meaning,
ecological validity)
What other factors are likely to modify
the chosen outcomes?
Outcome Measures (cont.)
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The same treatment may be judged
effective or ineffective, depending on
the outcomes chosen, e.g. case
examples mentioned earlier:
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Oral antispasticity medications
Memory remediation treatments
Outcome Measures (cont.)
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Should a cognitive rehabilitation
intervention have impact on:
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Patterns of brain imaging associated with
specific tasks?
Neuropsychological test scores?
Real-world activities similar to those used in
treatment?
Real-world activities different from those used
in treatment?
Real-world activities, performed under
distraction?
Overall Study Design
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Does the proposed mechanism of action
suggest a permanent effect of intervention?
(parallel group vs. crossover design)
Does the proposed mechanism of action
suggest “localized” or “generalized” treatment
impacts? (feasibility of multiple baseline
across behaviors design; utility of multiple
outcomes)
Study Design (cont.)
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Does the proposed treatment capitalize
on neurologic recovery (early vs. late
enrollment)?
Are there important covariates that
might affect treatment response that
should be measured?
Summary
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Published rehabilitation research frequently
fails to clearly describe who should benefit
from which treatment ingredients, with
respect to what outcomes
Theory-based treatment research has many
benefits, but among them is the ability to
optimize the selection of participants,
outcomes, and study design
Specifying the mechanism also leads the
way toward conceptualizing
interrelationships among treatment
outcomes
Summary (cont.)
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ICF provides a “meta-theory” for all
treatment research, though this theory
needs to be refined into a quantitative
model.
ICF predicts where we will see impact of
treatments that are effective but it
doesn’t give us effective treatments.
Summary (cont.)
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Focused domain-specific theories
provide tools for implementing change
at the organ, person, or societal level.
Only programmatic research can refine
the interrelationships among
measurement of patient characteristics,
therapy ingredients, and meaningful
outcomes.