Lead Investigator: Ramona Belfiore-Oshan, Critical Path Institute
Title of Proposal Research: Bayesian item response theory model for the North Star Ambulatory Assessment (NSAA) rating scale
Vivli Data Request: 10047
Funding Source: Critical Path Institute is supported by the Food and Drug Administration (FDA) of the Department of Health and Human Services (HHS) and is 54% funded by the FDA/HHS, totaling $19,436,549, and 46% funded by non-government source(s), totaling $16,373,368. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement by, FDA/HHS or the U.S. Government.
D-RSC is partially funded through a collaborative grant from Parent Project Muscular Dystrophy.
D-RSC is partially funded by membership fees paid by the member companies, who pay an annual membership fee to be a part of the consortium.
Potential Conflicts of Interest: Dr. Belfiore-Oshan reports: D-RSC is a non-profit consortium developing drug development tools that are suitable for regulatory uses. The consortium is supported by financial contributions of 12 drug companies, Parent Project Muscular Dystrophy and CureDuchenne, which contribute to the intellectual development of consortium projects. Companies are not permitted under the user agreement to discuss individual drug programs, and all results are made publicly available after submission to the regulatory authorities (FDA and EMA).
Dr. Zhang reports: – Data assembly and curation will be done in C-Path laptops and C-path cloud platforms. C-Path SOPs will be applied for data security. – Currently managing multiple projects from different C-Path consortia. C-Path SOPs will be applied to insulate data and information leakage to other projects.
Dr. Quinlan reports: – Data assembly and curation will be done in C-Path laptops and C-path cloud platforms. C-Path SOPs will be applied for data security. – Currently managing multiple projects from different C-Path consortia. C-Path SOPs will be applied to insulate data and information leakage to other projects.
Dr. Cunicelli reports: Potential: Current student at University of Arizona Dept of Biostatistics- Data/Research will be conducted on separate computers. Research has minimal overlap with proposed study. Potential: Current researcher at University of Arizona College of Nursing – Data/Research will be conducted on separate computers. Research has minimal overlap with proposed study
Summary of the Proposed Research:
Background
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness affecting approximately 1 in 3,500 male births worldwide. Recent advances in research for Duchenne muscular dystrophy DMD have resulted in a robust pipeline of drugs in development to treat the disease, along with the first drug approvals. Unfortunately, only a few recent drug trials have showed a statistically significant change in its primary outcome, causing discussion in the field as to whether drugs recently tested were effective or not. These controversies could be resolved through a comprehensive understanding of the longitudinal disease dynamics across appropriate measures, which could also be used to optimize future clinical trial design. Optimized trial protocols that convincingly determine if a therapy works or not are needed.
However, developing robust clinical trials in DMD is challenging due to several factors:
• DMD is a rare disease, so the population of individuals available to enter trials is small, confounded further by the number of concurrent trials being run.
• DMD is a progressive disease, such that endpoints that are appropriate at some disease stages (e.g. measures of ambulation/movement) may not be adequate or measurable at
other disease stages or across the disease spectrum. No endpoint has been developed that covers the entire disease continuum. This further limits the population
available for some trials, as well as making it difficult to ascertain whether a drug is effective at all stages of disease.
• DMD affects children, who are still growing and developing. Thus, in early stages of disease, individuals may gain strength and function, while in the longer term the
disease will result in loss of that function. Loss of function is also non-linear due to the fact that most functional tests are affected by the motivation of the subject on a given
day. Furthermore, events such as leg fractures (which are common in DMD boys) cause a temporary loss of a function that may be regained when the injury heals.
• DMD progression is variable, with different individuals progressing at different rates, although all individuals eventually lose function in a predictable order of events.
A clear need to improve understanding of the outcome measures persists. The North Star Ambulatory Assessment (NSAA) is a popular clinical outcome to assess the ambulatory metric of DMD patients. Improving the understanding of NSAA, in particular the discrimination (how rapidly the odds of getting one rating changes according to patient ability) and difficulty of each item will improve interpreting assessment results, gaining insights the relation between the outcome and disease state, and allowing more informed decision making in the drug development process.
Proposed model
We propose a hierarchical item response theory (IRT) model that evaluates the performance of North Star Ambulatory Assessment (NSAA) items.
Requested Studies:
A Prospective Natural History Study of Progression of Physical Impairment, Activity Limitation and Quality of Life in Duchenne Muscular Dystrophy.
Data Contributor: CureDuchenne
Study ID: NCT01753804
Sponsor ID: PRO-DMD-01
A Phase III, Randomized, Double Blind, Placebo-controlled Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
Data Contributor: CureDuchenne
Study ID: NCT01254019
Sponsor ID: 114044
A Phase II, Double Blind, Exploratory, Parallel-group, Placebocontrolled Clinical Study to Assess Two Dosing Regimens of GSK2402968 for Efficacy, Safety, Tolerability and Pharmacokinetics in Ambulant Subjects With Duchenne Muscular Dystrophy
Data Contributor: CureDuchenne
Study ID: NCT01153932
Sponsor ID: 114117
An Exploratory Study to Assess Two Doses of GSK2402968 in the Treatment of Ambulant Boys With Duchenne Muscular Dystrophy
Data Contributor: CureDuchenne
Study ID: NCT01462292
Sponsor ID: 114876