Substantial progress was reviewed at the third annual workshop of the National MS Society-supported MS Outcome Assessments Consortium in Washington, DC in late March. The MSOAC is a global effort aimed at developing a new tool that will address the critical need for a more sensitive way to detect the benefit of potential treatments that slow or reverse progressive disability in people with MS. Participants included representatives from academic institutions, pharmaceutical companies, the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the National Institutes of Health.
Over the 4-year, $3 million project, MSOAC is collecting data from many MS clinical trials, which will then be standardized and analyzed to identify the optimal measures for inclusion in this tool. This will then be submitted to the FDA and EMA for regulatory approval, a step toward validating its acceptance for use as a primary outcome measure in clinical trials.
Background: MSOAC was launched after a National MS Society-supported task force met in late 2011 to determine how to address the need for better measures of MS-related disability in clinical trials. The task force considered whether existing measures such as the MSFC (Multiple Sclerosis Functional Composite) could be enhanced or if one or more new measures would be needed. The task force determined that a key aspect of the project would be the need to analyze data from completed clinical trials that have used parts of the MSFC as well as other measures of disability.
After considering several options for implementing the goals of the project, it became clear that collaborating with the Critical Path Institute (C-Path) would be of great value. C-Path is a nonprofit partnership with the FDA, whose aim is to accelerate the pace and reduce the costs of medical product development by creating new standards for evaluating the safety and effectiveness of therapies.
Progress: Task Forces have been established and have been working, largely on a voluntary basis, to complete many steps needed to drive this effort. These include:
Data collection: Significant progress has been made in obtaining clinical trial data from industry and academic studies that used elements of the MSFC and other disability measures such as “low contrast visual acuity” (a highly sensitive way to evaluate visual problems) and the “symbol digit modalities test” (which measures cognitive processing speed). To date the team has amassed data from 17 clinical trials involving nearly 15,000 people with MS who participated in trials, with data from several additional trials being acquired. Ideally, the existing data may be sufficient to achieve the goals of the project, but some additional research may also be needed.
Data standards: An early achievement of the project has been the development of new MS data standards – called CDISC standards. This permits the harmonization of data collected across different studies, and will be required by the FDA for future clinical trials.
Patient Viewpoint: A plan is being devised to engage and gain input from people living with MS to help determine whether the measures of disability that will be included in the tool are relevant to real life activities. For example, if one measure will be how quickly a person can walk a specific distance, how does that walking speed translate into daily life tasks such as grocery shopping, caring for children, or staying employed? The Task Force will use innovative methods such as the “Modified Delphi Process” to gain input and develop consensus.
Other Task Force activities include:
developing and submitting “briefing packages” periodically to the FDA and EMA to gain feedback about specific aspects of the proposed disability measurement tool;
conducting a literature search of an estimated 1800 published papers to gather evidence supporting how the disability measures are best used and their relevance to individuals’ day to day activities;
creating a statistical analysis plan that will allow mining of data from clinical trials to develop the best disability measurement tool;
establishing a plan to make portions of the collected clinical trials data available to the larger research community.
As was the case for the previous annual workshops held at the FDA, this year’s workshop was well-attended by actively engaged FDA staff, who provided encouragement and valuable direction.
“Momentum is building, and the commitment of members is stronger than ever before,” commented Richard Rudick, MD (Biogen), co-director of MSOAC. “We’ve all come together and we’re all pulling in the same direction because we want to make progress for our patients and relieve human suffering.”
Future Activities: The Consortium is continuing the process of collecting data from completed clinical trials. Progress will continue toward compiling this data and analyzing it to evaluate potential components of a new outcome measure. Regular teleconferences are helping to keep this project moving. Ultimately, the proposed tool will be submitted to regulatory authorities for qualification as a primary outcome measure in MS trials. Upon qualification, the tool will be freely available, and details describing how to use the tool will be published.
Read more about MSOAC.