SBIR-STTR Award

Clinical trials of new medications often rely on subjective, observer-based ratings of side effects in the form of movement abnormalities to evaluate safety and tolerance of medication dosage. Imprecise ratings of adverse side effects have led to inconsistent results from these trials. Well-known adverse effects are extrapyramidal motor side effects (EPS), which can emerge within days of beginning treatment of antipsychotic drugs to treat schizophrenia, especially in the elderly. EPS symptoms include abnormalities in velocity scaling (VS) and force steadiness and smoothness (FS), which can be identified in handwriting movements. The symptoms are similar to those found in Parkinson's disease and dyskinesia. We propose to develop an easy-to-use, quantitative system for monitoring drug-induced EPS. In Phase I we will extend our existing handwriting movement analysis system to measure VS and FS. The resultant system will be used to conduct 4 experiments where we compare a group of schizophrenic patients with a group of healthy controls to verify that: (1) all subjects are able to perform the handwriting tasks sufficiently well with little instruction and practice; (2) variability over repeated measures of the handwriting task is acceptable; (3) demographic variables that significantly affect VS and FS scores can be minimized; and (4) the measurement procedure is valid by exhibiting high correlations with scores from observer-based severity ratings and conventional, complex instrumental measures. This research will lead to the application of movement analysis as a reliable and valid tool for evaluating medication effects, for use by the pharmaceutical industry, mental health clinics, and research laboratories throughout the world. Our system will help to reduce research and development costs, as adverse effects of new medications may be measured in a simpler and quicker manner than current methods. Additionally, patients and their families will benefit from enhanced monitoring of the adverse reactions associated with antipsychotic medication usage.

Thesaurus Terms:
abnormal involuntary movement, antipsychotic agent, computer program /software, computer system design /evaluation, drug adverse effect, extrapyramidal disorder, patient monitoring device, psychomotor function, schizophrenia antidepressant clinical research, human subject, neuropsychological test

Clinical trials of new medications often rely on subjective, observer-based ratings of side effects in the form of movement abnormalities to evaluate safety and tolerance of medication dosage. Imprecise ratings of adverse side effects have led to inconsistent results from these trials. Well-known adverse effects are extrapyramidal motor side effects (EPS), which can emerge within days of beginning treatment of antipsychotic drugs to treat schizophrenia, especially in the elderly. EPS symptoms include abnormalities in velocity scaling (VS) and motor steadiness or smoothness. We have shown in Phase I of this programmatic research that a system can be developed to reliably quantify these motor impairments during handwriting. In Phase II, we plan to expand the research started in Phase I toward developing an easy-to-use, quantitative system for monitoring drug-induced EPS. Specifically, the primary goals of Phase II are to conduct large- scale studies across several laboratories and clinics to examine generalizability of the measuring procedure and to examine the influence of treatment- and subject-related factors on outcome variables. The Phase II research plan consists of four experiments: (1) to examine effects of treatment-related variables on fine motor control during handwriting; (2) to examine effects of subject-related variables, such as demographics, and psychopathology on fine motor control during handwriting; (3) to examine the effects of task complexity on fine motor control during handwriting; and (4) to examine the generalizability of our findings across sites. Our long-term goal is to develop a general-purpose system for large-scale clinical trials that can readily be adopted in multi-center, clinical trials evaluating new drug safety and tolerance. From the perspective of the clinician, our handwriting movement analysis system will be a practical tool for screening and monitoring medication side effects in a variety of inpatient and outpatient neuropsychiatric settings. From an industry and governmental perspective, drug development will benefit from reliable and valid tools for assessing medication-induced side effects. The pharmaceutical industry would be able to reduce research and development costs if adverse effects of new medications could be measured quicker and more reliably than conventional methods.

Thesaurus Terms:
abnormal involuntary movement, antipsychotic agent, computer assisted medical decision making, computer system design /evaluation, drug adverse effect, extrapyramidal disorder, patient monitoring device, psychomotor function, psychopharmacology, schizophrenia antidepressant, biomechanics, computer program /software, tardive dyskinesia clinical research, human subject, neuropsychological test