Randomized control trials in ALS: lessons learned

As we stated in the Preface, a major impetus for organizing the ALS Clinical Trial Meeting held in Tarrytown, New York, was the overall great frustration we have had in treating ALS; that is, since 1996 when riluzole received FDA approval, we have not identified any new medications for ALS. Although we have been prescribing riluzole, its efficacy is modest at best. We desperately need more effective drugs. Although a cure may come only after the cause of ALS is elucidated, we do not have the luxury of waiting when we are confronted by the progressive paralysis of our patients. Vigorous basic research in ALS has offered new hypotheses and opportunities to test novel drugs. In the past two decades, we have had more than 25 randomized clinical trials (RCTs) in ALS (Table 1). Although we surely have made great progress in these trials, the collective experience is still less than that in many other diseases. An important lesson is always to learn from others and from the past. We have therefore decided to provide here not a review but rather an overview of the collective experience in past ALS RCTs, which hopefully will serve as a useful Introduction to this supplement. The issues that we raise are examined in detail by the other contributors to the supplement.