The overarching goal of this proposal is to accelerate recruitment for clinical trials in a rare autoimmune disease, myositis, and to improve the current outcome measures for assessing treatment response by incorporating robust patient-reported outcomes and practical functional measures as metrics of response to future therapies. This approach addresses critical gaps in the conduct of myositis clinical trials: (1) Poor subject recruitment that geographically disenfranchises many myositis patients; (2) Lack of relevant patient-reported outcomes as a response metric to available therapies; and (3) Paucity of practical functional measures to longitudinally assess outcome in myositis patients with muscle weakness. Our goal is to establish a national cohort of myositis patients without geographic restriction using state-of-the-art technology (smart phone mobile applications and the web) coupled with tele-medicine techniques (tele-research) and to validate: (1) patient- reported metrics of PROMIS-physical function and (2) quantifiable metrics of functional outcome from physical activity monitors.
Specific Aim 1 will establish the superiority of recruitment and enrollment of a tele-research cohort (TRC) compared to a myositis center-based cohort (CBC) while at the same time demonstrating that data collection and data integrity is uncompromised in the TRC compared to the CBC. This strategy can then be applied to future myositis clinical trials by enlisting the support of commercial laboratories for bio-specimen collection and mobile research units for drug delivery and trial monitoring activities. In addition, we have incorporated rigorous qualitative analysies to understand patients' perceptions and barriers towards myositis clinical trials using tele-research as compared to a center based approach. This will address key gaps in our knowledge and approach, ultimately leading to more effective and efficient clinical trial design in rare diseases.
Specific Aim 2 a will test the reliability, validity, and responsiveness of physical activity monitors as a novel functional and objective outcome measure in future myositis trials and Specific Aim 2b will address the reliability, validity, and responsiveness of PROMIS-physical function computer adaptive testing and the efficiency gained over the current patient-reported measures employed in myositis observational studies and clinical trials. The University of Pittsburgh Myositis Center has an excellent track record of successful observational studies and clinical trials and our preliminary data demonstrates the feasibility, capability, and proof of concept for all of the proposed measures. We have an established team of investigators with experience in myositis clinical trials, outcome measures along with expertise in qualitative analysis, website design and management, PROMIS and physical activity monitors. All of our data is stored in a robust prospective database that incorporates patient consenting, all forms of data entry and analysis, a modular approach to experimental protocols, and data extraction and analysis capabilities. The knowledge gained from the proposal will be invaluable to any future clinical trial in myositis.
Myositis is a rare, systemic, autoimmune disease with considerable morbidity and mortality that affects 100- 200 of every 1 million Americans. To date, there have been few clinical trials and no FDA-approved therapies in myositis. The objective of this proposal is to use state-of-the-art technology in an innovative approach to patient recruitment for future clinical trials and to test practical and relevant patient-reported outcomes and functional measures as benchmarks of response to myositis therapies.