Portal de Periódicos da CAPES

Concerns about the design of clinical trials for spinal muscular atrophy

2004; Elsevier BV; Volume: 14; Issue: 8-9 Linguagem: Inglês

10.1016/j.nmd.2004.04.004

1873-2364

Tyler Crawford,

Congenital Anomalies and Fetal Surgery

The distinctive clinical course of SMA, characterized by slowing of the rate of degeneration with the passage of time, presents a special challenge to therapeutic clinical trial planning. Much of the actual functional decline may represent either an inevitable consequence of growth or the result of various secondary complications of weakness, making the study of agents intended to improve the course by increasing the level of SMN protein that much more difficult. Studies intended to demonstrate a slowing of the rate of degeneration, modeled upon clinical trials for ALS, are problematic. In contrast, short-term trials designed to demonstrate improved strength have substantial design advantages, but depend upon the demonstration of salutary effects of increased SMN that are plausible but at present only theoretical. This form of study thus has some potential for type II error, falsely rejecting a useful drug. Despite this limitation, logistic and statistical concerns suggest that the best strategy for evaluating any promising new therapy will be to use first a short-term study.