The Eaton Collaborative Study Of Levodopa Therapy In Parkinsonism

THE DRAMATIC DISCOVERY by Cotzias et al.1 in 1967 shifted the Eaton effort in the parkinsonism area from anticholinergic compounds to levodopa. After preliminary animal tests and a complete review of the literature, the Eaton Collaborative Study (ECS) was undertaken to determine the safety and efficacy of orally administered levodopa in a selected group of patients with parkinsonism by a group of clinicians who discussed and agreed upon a uniform protocol and a single case history form. Physician members of the ECS were selected on the bases of competence in neurology and geographic location. A reasonable geographic cross section was felt to be desirable. Only Board-certified or Board-eligible clinicians were included, and about half of these were already experienced in the use of levodopa. Of the 22 clinicians listed in Table 1, 16 have contributed to the data which will be presented here. The others have undertaken strict double-blind or other special studies to be reported later. The ECS plan was arbitrarily divided into 4 periods. Patients were admitted into the study without regard to age, sex, or severity or duration of disease. After a preliminary period of observation on their previous drug regimen (period l), selected patients were given placebo capsules (period 2 ) . The clinical functions and laboratory values that were measured during the levodopa trial were also measured on the previous drug regimen and during the placebo regimen, where applicable. After an optimal dose of levodopa was established (period 3) , periodic follow-up assessments were carried out (period 4). Upon admission into the* ECS, each patient was identified according to age, sex, race, and the type, duration, and severity of parkinsonism. Severity was graded according to the criteria of Hoehn and Yahr:2 grade I, unilateral involvement; grade 11, bilateral; grade 111, first evidence of impaired balance; grade IV, fully developed severe disease; and grade V, confinement to bed or wheelchair unless aided. The rated neurological examination developed by Yahr et al.3 was modified and utilized as a measure of the effectiveness of levodopa in each period. All the major signs and symptoms of parkinsonism were evaluated, including mental status; postural stability; sialorrhea; sweating; facial expression; bradykinesia; right and left finger dexterity; tremor of each extremity, face, and lips; rigidity of each extremity and neck; and posture. Each sign or symptom was rated numerically on a carefully defined scale to assure maximum agreement between the collaborative investigators: 0 = absent, 1 = slight and infrequently present, 2 = moderate in amplitude but present only intermittently, 3 = moderate and present most of the time, 4 = marked in amplitude and present most of the time, and x = not tested. The sum of the scores for each patient provided an index of the severity of his illness. In each of the 4 periods, the Northwestern University Disability Scale devised by Canter et aL4 was used to assess the performance of daily living activities. This scale enabled each clinician to measure such common activities as walking, dressing, eating, feeding, hygiene, and