Over the past two decades, the El Escorial criteria (EEC) have been used as eligibility criteria in major randomized controlled trials. One of the goals of the revised EEC was to allow earlier diagnosis and, thus earlier trial inclusion by introducing a new category, namely "clinically probable laboratory supported" ALS. This category allowed EMG findings to be taken into account assuming that EMG is more sensitive than the clinical examination in detecting lower motor neuron signs. Recently, Edaravone has been licensed in several countries for the treatment of ALS based on a randomized controlled trial in a selected group of ALS patients excluding the EEC category "clinically probable laboratory supported". The major reason was that in a post hoc analysis of the first Edaravone trial this group comprised many slow progressors. As it is unclear whether this bias towardslow progressors was a study-specific problem or related to the category itself, we performed an analysis in the PRO-ACT dataset. In the PRO-ACT dataset, progression in ALS patients included at baseline into the "clinically probable laboratory supported" category was significantly slower (-0.53 in ALSFRS/month) compared to the other EEC categories (-0.68 in ALSFRS/month; p < 0.001) and exhibited a significantly longer diagnostic delay (13.5 months vs. 11.7 months, p < 0.001). This suggests that the bias toward slow progressors in the "clinically probable laboratory supported" category is an inherent problem of the category and thus does not fulfill the previous goal of earlier diagnosis, raising several questions concerning the application of this category.

中文翻译：

---

修订后的El Escorial标准“临床上可能由实验室支持的ALS”-曾经是一个有希望的现在多余的类别吗？

在过去的二十年中，El Escorial标准（EEC）被用作大型随机对照试验的资格标准。修订后的EEC的目标之一是允许通过引入新类别（即“临床上可能由实验室支持的” ALS）来进行早期诊断，从而早期纳入试验。假定EMG在检测下运动神经元体征方面比临床检查更为灵敏，因此可以考虑到EMG的发现。最近，依达拉酮已在多个国家/地区获得了基于ALS的随机对照试验的ALS治疗许可，该研究针对一组选定的ALS患者，但不包括EEC类别“临床可能的实验室支持”。主要原因是，在对第一个Edaravone试验的事后分析中，该组包括许多进展缓慢的患者。由于尚不清楚这种偏向低进展者的偏向是针对研究的问题还是与类别本身有关，因此我们在PRO-ACT数据集中进行了分析。在PRO-ACT数据集中，与其他EEC类别（ALSFRS /月为-0.68； p < 0.001），并显示出明显更长的诊断延迟时间（13.5个月vs. 11.7个月，p <0.001）。这表明在“临床上可能由实验室支持”类别中偏向于进展缓慢的偏倚是该类别的固有问题，因此不能满足早期诊断的先前目标，从而引发了有关该类别应用的若干问题。