Amitriptyline to relieve pain in juvenile idiopathic arthritis: a pilot study using Bayesian metaanalysis of multiple N-of-1 clinical trials.
OBJECTIVE
Using serial N-of-1 trials and subsequent analysis with Bayesian methods may allow study of therapies using small numbers of subjects. Our research questions were: (1) Can serial N-of-1 trials analyzed with Bayesian statistical techniques be used to estimate the population effect of a therapeutic intervention? (2) Compared to placebo, how likely is it that low-dose amitriptyline therapy in children aged 10-18 years with active polyarticular-course juvenile idiopathic arthritis (JIA) results in a significant improvement in pain?


METHODS
Six children (age 10.3-16.3 yrs, 4 girls) were enrolled. There were 3 pairs of randomized, double-blinded treatments (amitriptyline 25 mg or placebo) per participant. Each treatment lasted 2 weeks, with a 1 week washout. The primary outcome was pain, measured by 10 cm visual analog scale. Assessments were at the beginning and end of each treatment. A Bayesian statistical model was used to determine the treatment effect. Values < 0 indicated superiority of amitriptyline.


RESULTS
Bayesian techniques were used successfully to obtain estimates of population effect, despite the small number of participants. The mean treatment effect for pain was 0.67 (SD 0.89, 95% credible interval -0.99, 2.55). The probability that the treatment effect was < 0 was only 16%.


CONCLUSIONS
These methods can be used successfully to estimate population effects when sample sizes are small. It is unlikely that amitriptyline reduced pain by a clinically significant amount in these children with polyarticular JIA. These methods may be particularly suited to pilot studies and the study of rare illnesses.
Huber
Adam M
AM
Division of Pediatric Rheumatology, IWK Health Centre and Dalhousie University, Halifax, Nova Scotia, Canada. adam.huber@iwk.nshealth.ca
Tomlinson
George A
GA
Koren
Gideon
G
Feldman
Brian M
BM
D000293:Adolescent; D000639:Amitriptyline / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D001499:Bayes Theorem; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010147:Pain Measurement; D010865:Pilot Projects; D018401:Sample Size; D016896:Treatment Outcome
D018712:Analgesics, Non-Narcotic; D000639:Amitriptyline