1. MODELS OF REHABILITATION RESEARCH John Whyte, MD, PhD Moss Rehabilitation Research Institute & Thomas Jefferson University

2. The ICF & Related Models Body structure (disease) Body function (impairment) Activity (disability) Participation (handicap)

3. Biomedical Research Deals primarily with body structure & function Assumes that functional ability is directly related to resolution of body structure/ function abnormalities What about….. Improvement in function w/o improvement in pathology? Improvement in pathology w/o improvement in function?

4. Sustained Attention Working Memory Language Comprehen- sion Balance Motor Coordination Diffuse Axonal Injury Contusion Sensori- neural Hearing Loss Diabetic Neuropathy Driving Public Speaking ParentingEmployment Body Structure Body Function Activity Participation

5. Levels of Intervention

6. Implications for Research 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

7. 2 Case Examples The effects of oral antispasticity medications (Whyte & Robinson, 1990) The effects of cognitive remediation (Carney, et al, 1999; Cicerone, et al, 2000)

8. Implications for Training 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?

9. Using Theory In Rehabilitation Research 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?

10. Key Elements in Efficacy Study Design Defining the appropriate study sample Defining the “active ingredients” of treatment Defining the study outcomes Determining the overall study design

11. What do we mean by “treatment theory”? A proposed specification of the “active ingredients” of treatment A proposed specification of the mechanism of action of those active ingredients

12. Why do we need a treatment theory? 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

13. Multifaceted Treatments 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?

14. Reducing the Infinite 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

15. Theory Development 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 motor- lesioned monkeys)

16. Treatment Theory Can Inform Other Aspects of Study Design Selection of appropriate study participants Selection of appropriate outcome measures Selection of the optimal experimental design

17. Study Participants Given the proposed mechanism of action, who can realistically benefit? 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)

18. Study Participants (cont.) Choose participants that vary in the the hypothesized “treatment responsive” characteristics to clarify the mechanism? 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

19. Characterizing the Participants Once selected, one must ask whether the participants in different treatment groups are “comparable” – comparable in what way(s)? Balance achieved between randomized groups Statistical adjustment of differences in observational studies Need prior data on prognostic factors

20. Comparability & Adjustment 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

21. Outcome Measures Given the proposed mechanism of action of the treatment, where would you expect to see treatment impact? 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?

22. Outcome Measures (cont.) The same treatment may be judged effective or ineffective, depending on the outcomes chosen, e.g. case examples mentioned earlier: Oral antispasticity medications Memory remediation treatments

23. Outcome Measures (cont.) Should a cognitive rehabilitation intervention have impact on: 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?

24. Overall Study Design 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)

25. Study Design (cont.) 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?

26. Summary 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

27. Summary (cont.) 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.

28. Summary (cont.) 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.