CONTINUOUS RESPONSE VARIABLE TRIAL DESIGN IN MOTOR-NEURON DISEASE - LONG-TERM TREATMENT WITH A TRH ANALOG (RX77368)

The continuous response variable controlled trial design is developed as a model for the efficient screening of candidate treatments in moto r neuron disease. A TRH analogue (RX77368) and placebo were randomly a llocated to 15 matched pairs of patients with motor neuron disease. Wi th validated composite interval scores, this trial excluded a 50% or g reater improvement with RX77368 at month 12 in scores of respiratory, lower limb, and activities of daily living function with greater than 90% power, and in bulbar function scores with 80% power. For upper lim bs, 52% and 75% improvements were excluded at months 9 and 12 respecti vely with 80% power. Patients who died during the study had faster det erioration rates in bulbar and respiratory scores than their surviving pairs. The feasibility of screening drugs for significant biological effects with small sample sizes and good statistical power is shown. T he difficulties of handling deaths and dropouts when using this design are discussed. Comparisons are made with sample sizes required using other scores and rating scales, as well as with those required in haza rd and event rate studies. A simple clinical grading scale for motor n euron disease, with its corresponding composite interval scores, is de scribed.