Lancet Neurol. 2013 Nov;12(11):1037-8. doi: 10.1016/S1474-4422(13)70224-2. Epub 2013 Sep 23.

The murky path to drug discovery in ALS becomes clearer.

Gordon PH.

Source

Northern Navajo Medical Center, Highway 491 North Shiprock, NM 87420, USA. Electronic address: paul.gordon@psl.aphp.fr.

"The blueprint exists.^{9, 10, 11 and 12} Phase 2 trial designs aimed at reliable dose selection have been done in other neurological diseases and in ALS.^{10, 12 and 13} A selection model chooses the best of several arms (ie, drugs, doses, interventions) on the basis of statistical probability instead of evidence of significant efficacy.¹² When a futility comparison is added to determine whether testing of the selected dose is justified, the entire phase 2 selection-futility trial requires many fewer patients than does a standard design.¹³ Some researchers contend that a low threshold for declaring non-futility is susceptible to error, but history shows that it is the standard parallel phase 2 trial that demonstrates erroneous efficacy outcomes in ALS. The advantages of the selection-futility trial are efficiency and testable hypotheses suited to small sample size. The high quality, great expenditure of resources, and discouraging outcome of EMPOWER bring clarity to the underappreciated role of the phase 2 trial in ALS. Efficient dose selection is a beacon on the murky path to drug development in ALS."