Article Text

Download PDFPDF
Two heads are better than one: benefits of joint models for ALS trials
  1. Ruben P A van Eijk1,2,
  2. James Rooney3,
  3. Orla Hardiman3,4,
  4. Leonard H van den Berg1
  1. 1 Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2 Biostatistics & Research Support, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  3. 3 Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
  4. 4 Neurology, Beaumont Hospital, Dublin, Ireland5
  1. Correspondence to Dr Ruben P A van Eijk, Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584, The Netherlands; R.P.A.vanEijk-2{at}

Statistics from

Kaji et al recently conducted a phase II/III clinical trial to evaluate the safety and efficacy of methylcobalamin in 343 patients with amyotrophic lateral sclerosis (ALS).1 Both coprimary endpoints (survival and ALS Functional Rating Scale [ALSFRS-R]) failed to show significant benefit (p=0.19 and p=0.13, respectively). The choice for two coprimary endpoints is interesting and may have circumvented important pitfalls encountered by previous ALS trials.2 As ALS significantly reduces the patient’s life expectancy, evaluating a drug’s therapeutic potential to improve survival is fundamental. Survival time, however, may be influenced by life-extending interventions (eg, gastrostomy or tracheostomy) and provides little information about the patient’s functioning during life. The ALSFRS-R is a welcome alternative that is clinically relevant, easily obtained and highly predictive of survival time. Unfortunately, positive phase II results on the ALSFRS-R have until now …

View Full Text

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.