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Comment & Response
April 29, 2019

Proper or Improper Use of the Crossover Design in Clinical Trials in Chronic Sciatica?

Author Affiliations
  • 1Department of Neurosciences and Mental Health, Neurology, Hospital de Santa Maria, CHULN, Lisbon, Portugal
  • 2Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
JAMA Neurol. 2019;76(6):731. doi:10.1001/jamaneurol.2019.0870

To the Editor Robertson et al1 conducted a crossover randomized clinical trial of gabapentin (GBP) vs pregabalin (PBG) in chronic sciatica (CS). We congratulate the authors for their effort toward improving CS management. However, some methodological issues hinder the conclusions in this trial.

First, we believe that a crossover design may be inappropriate to answer the question of interest. Crossover trials assume that the disease is stable and the effects of an intervention do not carry over from one period to the next. Chronic sciatica intensity fluctuates over time and the 1-week washout period may be insufficient, meaning that the observed effects may be attributable to a longer clinical effect or the disease course and not exclusively to the differences between GBP and PBG. More important than surpassing a given number of half-lives, a preliminary test for differential carryover effects between the drugs should be made and the sequence and period effects should be accounted for to ensure washout period adequacy. Otherwise, the carryover effect is not excluded and only the first parallel phase of the study can be interpreted.