Table 2.

Consideration of causality of adverse events and expectedness in the course of ALS

Assessment of causality
• Temporal association between the administration of the investigational product and the event • Cessation of the AE following discontinuation of dosing • Recurrence of the AE with reintroduction of study drug, if performed • Similarity to known class effects • Alternative causes, such as known effects of concomitant medications   − Pre-existing risk factors   − Concurrent illnesses
Assessment of expectedness: based on Medical Dictionary for Regulatory Activities (MedDRA)
Dysarthria Dysphagia Dyspnea Gait disturbance Involuntary muscle contractions Muscle spasms	Muscle spasticity Muscle weakness Muscle stiffness Pneumonia aspiration Respiratory failure Weight loss