Historical controls in ALS trials

Abstract

In Coleridge's poem “Rime of the Ancient Mariner,” the lost crew laments their plight: > Water, water, every where, > > And all the boards did shrink; > > Water, water, every where, > > Nor any drop to drink. This famous verse could also describe the current state of clinical research in amyotrophic lateral sclerosis (ALS). While for years the landscape was more like a “desert,” we now have an “ocean” of potential ALS therapies moving into clinical trials. Unfortunately, the rarity of ALS and the historically low enrollment rate in ALS trials1 will challenge efficient completion of these, prolonging our “thirst” for better disease-modifying therapies. New types of ALS trials, especially those that would be more resource-efficient or attractive to patients with ALS, may provide a “rescue.” Along such lines, Miller and associates2 herein report the third lithium trial failing to slow disease progression in ALS. The most interesting aspect of this phase II screening study was the use of historical controls; the authors matched their subjects, all of whom received lithium, against 249 placebo controls from the minocycline in ALS trial (MINO).3 This design feature may allow a smaller sample size. Also, by ensuring that every patient receives drug, it likely makes the …