North American Clinical Trials Network (NACTN)
The Reeve Foundation's Neurological Outcomes Assessments (NOA) Task Force, an integral part of the North American Clinical Trials Network (NACTN), has begun the much-needed work to develop, test and validate improved outcome measures for use in human clinical trials of spinal cord injury.
"Clinical trials and therapies for SCI are being implemented and may be doomed to fail without appropriate outcome measures to demonstrate that the successes in animals can be translated to humans," said NACTN Principal Investigator Robert G. Grossman, M.D. "Our goal is to develop sensitive outcome measures for SCI and to expedite their use clinically."
Grossman added that in the long-term, treatments will probably come in a series, "including therapies directed at neuroprotection, glial scar, modulation of nervous system, regenerative therapy, plasticity therapy and so on. No single approach is likely to have dramatic effects."
ASIA Impairment Scale
The most common outcome assessment tool for SCI in use today is the ASIA Impairment Scale (AIS, from the doctors' group, American Spinal Injury Association). But this test, which measures neurological level of injury, was never meant to be used as an outcome measurement. It's not sensitive enough.
"Manual muscle testing in the AIS likely won't detect small changes that occur after a therapy," said Susan Harkema, Ph.D., from the University of Louisville and co-chair of the Task Force. Many of the therapies headed for clinical trial won't result in something as easy to spot as say, walking. "The worst thing that could happen is that an intervention could be successful and not show up on the measurement scales we have now."
Said Susan Howley, Reeve Foundation Executive VP, Research: "NOA is an extremely important initiative of the Foundation. We need reliable and sensitive measures that can detect small, incremental changes in patients."
Goals for the Task Force
The 25-member NOA group, representing experts from Europe, Canada and the United States, has met twice in recent months. The group agreed to pursue two categories of outcome instruments:
- those with the potential to be ready for use in clinical trials in 2010, and
- those that will take longer to develop and validate but have strong potential for accuracy and reliability.
The Task Force also agreed upon broad outcome areas: autonomic function (including measurement of changes in bowel, bladder and sexual function), motor function, pain and sensory response, and quality of life (meaningful changes reported by the patient).
Development of new tools to measure outcomes is a key part of the process. The NOA panel considered, for example, devices to better measure hand strength. "We need good hand function testing," said Harkema. "The AIS doesn't give us a lot of information regarding hand function." One hand-test possibility is a device called GRASSP (Graded Redefined Assessment of Strength, Sensibility, and Prehension), developed by scientists at the Universities of Toronto and Zurich, and partly funded by the Reeve Foundation. Another is QMAD (Quantitative Motor Assessment Device) from the Grossman group in Houston.
Several other ways to assess outcome are being considered, including the use of evoked potentials, myometry (measuring muscle tone), by using video recording over time, and by keeping track of autonomic progression (blood, bowel, bladder and sexual changes) Also, asking the patients the right kinds of questions can help assure better outcome assessment.