Stanford University


Grant Number: 2U01AR052158-06
Project Title: Improving Assessment of Physical Function and Drug Safety in Health and Disease
PI Name, Title and Contact Information: James Fries, MD, Principal Investigator, Professor of Medicine, Stanford University
Other Key Personnel: Bonnie Bruce, DrPH, MPH, RD, Administrator/Project Manager
Eswar Krishnan, MD, Co-Investigator
Matthias Rose MD, PhD, Co-Investigator
Web Site: http://aramis.stanford.edu

Abstract:

Patient reported Physical Function (or Disability) is an important component of clinical and epidemiological studies. The traditional instruments used to assess Physical Function have served us well over three decades, but the newer tools of Item Response Theory and Computerized Adaptive Testing now permit major improvements resulting in better power and precision. Our work with the Patient Reported Outcomes Measurement Information System (PROMIS) resulted in more powerful patient reported tools. However, this work has revealed critical yet unresolved issues– issues that we address in the current proposal. We have two specific aims:

AIM 1: To extend the Physical Function domain developed during PROMIS I to the ceiling and to the floor and to develop, test, and evaluate one subdomain related to Physical Functioning. This aim will result in tools that will enable equiprecise detection of changes in physical function among individuals with superior abilities ("Positive health") and among those with severe impairment or frailty ("Negative health"). Building upon our work in PROMIS I, we will develop and evaluate items for a related domain ("Performance of activities requiring physical function").

AIM 2: To test, calibrate and validate these domains in heterogeneous clinical populations. The test populations will be subjects who have rheumatoid arthritis (RA), hip and knee osteoarthritis, systemic lupus erythematosus (SLE), and gout. In addition, we will include the frail and severely impaired who live in nursing home settings and study individuals with unusually high functional abilities. We expect to collaborate with other Primary Research Sites (PRS) in the PROMIS effort and to extend physical function item calibration and testing to other important disease areas such as juvenile rheumatoid arthritis, cancer, scleroderma, heart failure, diabetes, and chronic obstructive pulmonary disease.

Availability of these tools will result in outcome assessment tools that will not be bounded by floors and ceilings, will be appropriate endpoints for the interventions being studied, will better represent the patient's perspective, and will enable more effective and more cost–effective clinical research.

GOALS:

Physical Function is a major patient reported outcomes (PRO) domain, and assessment has traditionally been performed using questionnaire instruments. These instruments (e.g., the Health Assessment Questionnaire [HAQ–DI and the PF–10 Short Form of the SF–36 health survey [SF–36] and their incremental modifications) over time have yielded sensitive and valid endpoints. Yet, the marginal benefit of incremental modification has not been large.

The tools of Item Response Theory (IRT) and Computerized Adaptive Testing (CAT) now permit major advances. IRT analyses identify items with the highest information content over a specific range of disease severity. CAT applications sequentially select items providing the maximum information for a subject based on previous responses. Together they increase precision and/or decrease the number of items required. The Patient Reported Outcomes Measurement Information System (PROMIS) was created under the NIH Roadmap to develop and disseminate improved outcome assessment tools for clinical research. Over the past 4 years, there has been considerable progress in developing short-form and dynamic tools based on IRT and/or CAT. However, these efforts also have revealed critical areas that require attention; these form the basis for this proposal.

We propose to extend the Physical Function domain into very difficult (Positive health) and very simple (Negative health) task areas to virtually eliminate the important problem of floor and ceiling effects and to develop and validate a sub–Physical Function "Performance" domain which assesses related but distinct latent traits.

For questions concerning Stanford University’s role in the PROMIS network, please contact James Fries, MD, by e-mail at jff@stanford.edu. For more information about the PROMIS network, go to http://www.nihpromis.org.