Rasch-Built Outcome Measures to Improve ALS Clinical Trials
Abstract
The goal of this project is to develop improved outcome measure tools that can be used to make ALS clinical trials more efficient, leading to faster discovery of treatments for ALS. Most ALS clinical trials test drugs that are intended to slow progression of disease. In order to do this, research studies must use reliable measures of disease progression so that changes in disease status are captured when changes have truly occurred. If the outcome measures used to track disease progression are not reliable or not responsive enough, then trials must include more patients for a longer period of time to monitor treatment response, slowing research progress. Use of unreliable outcome measures can also lead to trials with incorrect or inconclusive results, for example, failure to recognize treatment benefits that actually exist or the appearance of a drug benefit when the drug is not actually effective. Completion of this project is expected to lead to long-term benefits for all patients with ALS by improving the way clinical trials are performed in the future and therefore accelerating the treatment discovery process. The revised ALS Functional Rating Scale (ALSFRS-R) is the outcome measure used for many past and current ALS clinical trials, but prior studies have discovered numerous objective flaws and limitations with this scale that have important implications when the scale is used as the primary outcome for research studies. This proposal will refine and create outcome measures using the Rasch method, a modern test theory approach that applies a mathematically rigorous process to produce scales that outperform traditional ordinal scales. Recently, a new scale, the Rasch-built Overall ALS Disability Scale (ROADS), was created and validated, and this scale shows objective statistical advantages over the ALSFRS-R. The ROADS is a simple questionnaire that measures overall disability level and can be completed by patients with ALS in person or by telephone in about 5 minutes. For the first Aim in this proposal, the ROADS will be studied further to obtain the information that is needed to make the ROADS ready for use in clinical trials as a primary outcome measure. Planned analyses include examining how the ROADS changes over time in patients with ALS, discovering how scores on the ROADS compare to other important clinical outcomes, determining what degree of change on the ROADS is considered clinically meaningful by patients with ALS, confirming reliability for a web-based version of the ROADS, and validating ROADS performance in a broader group of patients with ALS. For the second Aim of this proposal, a new outcome measure will be created based on the bedside neurologic exam, also using the Rasch method. Patients with ALS undergo routine neurologic exams when they visit the clinic, when they are evaluated by telemedicine, or when they participate in study visit for research, but the valuable information collected for these exams is currently not collected in a quantified way. There is currently a missed opportunity to capture the assessments that are already being performed in a systematic manner so this information can be used to detect treatment effects in clinical trials and better understand how patients are progressing in the clinic. This proposal will create a new outcome measure based on the neurologic exam using the Rasch method to capture overall motor strength in patients with ALS. This scale will capture strength of the speech and swallowing muscles as well as muscles of the neck, trunk, arms, and legs through routine bedside examination techniques. This new scale can contribute to improving future ALS clinical trials by improving the ability to track disease progression in-person or through telemedicine assessments. Creation of an objective outcome measure for ALS that can be performed by telemedicine will be particularly valuable for conducting high-quality research and clinical care in the setting of an unpr
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110124
Entities
People
- Christina Fournier
Organizations
- Emory University
- United States Army