Personal view: a potential novel treatment for fatigue complicating chronic liver disease – how should its efficacy be evaluated?
Article first published online: 30 MAR 2006
Alimentary Pharmacology & Therapeutics
Volume 23, Issue 8, pages 1113–1116, April 2006
How to Cite
JONES, E. A. (2006), Personal view: a potential novel treatment for fatigue complicating chronic liver disease – how should its efficacy be evaluated?. Alimentary Pharmacology & Therapeutics, 23: 1113–1116. doi: 10.1111/j.1365-2036.2006.02862.x
- Issue published online: 30 MAR 2006
- Article first published online: 30 MAR 2006
- Publication data Submitted 27 December 2005 First decision 23 January 2006 Resubmitted 26 January 2006 Accepted 31 January 2006
Profound fatigue is a clinically significant complication of chronic liver disease. A mechanism of fatigue in experimental animals and male athletes appears to be increased serotoninergic neurotransmission in the brain. Recently, attempts have been made to assess the efficacy of a serotonin antagonist, specifically the 5-HT3 receptor subtype antagonist, ondansetron, in ameliorating fatigue in patients with chronic liver disease.
However, the results of a randomized controlled trial of ondansetron for fatigue in patients with primary biliary cirrhosis did not indicate that ondansetron was either effective or ineffective. The reasons for the uncertain outcome of the randomized controlled trial are not clear. One contributing factor may have been the use of subjective indices of fatigue as primary efficacy endpoints. There is a need to develop objective quantitative primary efficacy endpoints for use in trials of therapy for fatigue.
Another contributing factor may relate to the conduct of a randomized controlled trial not invariably being the optimal approach to resolve a specific clinical issue, particularly when the application of statistical methods yields equivocal findings. When the results of a randomized controlled trial are indecisive, findings based on clinical judgement, medicine's most important asset, should be carefully evaluated.