Issues in clinical trial design II

The Workshop Breakout Session on Selection of End Point Measures in ALS clinical trials at the Advances in Amyotrophic Lateral Sclerosis colloquium discussed several areas of clinical trial methodology that required further evaluation and development.

It was clear that choosing among drugs in the treatment of ALS will be difficult because drug efficacy has been based on different end point measures in different trials. To date, the large clinical or pivotal trials have been sponsored by pharmaceutical companies, with the primary and secondary end point measures evaluated in phase IIB clinical trials and selected with the help of consulting neurologists. The World Federation of Neurology (WFN) Research Group on Neuromuscular Diseases Subcommittee on Motor Neuron Diseases, as a neutral body, has been active in sponsoring workshops addressing concerns affecting entry into drug trials and selection of clinical trial end point measures. The initial workshop on "The Clinical Limits of ALS" at El Escorial European Conference Center near Madrid, Spain, proposed a set of diagnostic criteria, critically reviewed at the 1990 International Congress on Neuromuscular Diseases in Munich, Germany, that could be used at the entry point for clinical trials in multiple settings. The El Escorial WFN criteria for the diagnosis of ALS establish different levels of certainty for the diagnosis of ALS as a function of the diagnostic testing available. ^[1]

At the Orlando meeting, there was a strong consensus that it would be desirable to test drugs at the earliest stage of ALS, and that this is a challenge with the current use of "probable" and "definite" diagnostic levels of certainty used in clinical trials. It was pointed out that the El Escorial criteria allow for increasing the level of certainty by using diagnostic tests such as EMG and neuroimaging. The results of large trials suggest that few patients …