Journal of Neurology, Neurosurgery, and Psychiatry, 1995, Vol 58, 201-208
Continuous response variable trial design in motor neuron disease: long term treatment with a TRH analogue (RX77368)
A Goonetilleke and RJ Guiloff
Neuromuscular Unit, Charing Cross Hospital, London, UK.
The continuous response variable controlled trial design is developed as a
model for the efficient screening of candidate treatments in motor neuron
disease. A TRH analogue (RX77368) and placebo were randomly allocated to 15
matched pairs of patients with motor neuron disease. With validated
composite interval scores, this trial excluded a 50% or greater 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 limbs, 52% and 75%
improvements were excluded at months 9 and 12 respectively with 80% power.
Patients who died during the study had faster deterioration 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. The 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 hazard and event rate studies. A simple clinical
grading scale for motor neuron disease, with its corresponding composite
interval scores, is described.
