Lessons learned combining N-of-1 trials to assess fibromyalgia therapies.
OBJECTIVE
Applying population research to individual treatment requires understanding the connections between patient-specific characteristics, population-based studies, and treatment responses. Conducting practice-based research using individual-focused (N-of-1) trials may aid this process. We combined N-of-1 trials to compare fibromyalgia therapies and to assess the feasibility and outcomes of this approach for practice-based effectiveness research.


METHODS
Community- and center-based rheumatologists enrolled patients with fibromyalgia syndrome in randomized, double-blind, multi-crossover, N-of-1 trials comparing amitriptyline and the combination amitriptyline and fluoxetine. Fibromyalgia Impact Questionnaire outcomes were used for the individuals' treatment and combined across patients for sample-based analyses. Outcomes were compared with results from more standard trial designs.


RESULTS
Eight rheumatologists enrolled 58 patients in N-of-1 trials. Most physicians and patients had not previously participated in clinical trials. Using several analytic methods, the pooled results showed a better outcome score (mean difference: -6.1 +/- 2.0 to -8.0 +/- 3.7 points) in patients taking combination therapy. These population results are similar to published outcomes from a more traditional crossover trial. Neither practice type nor patient characteristics were significantly associated with the observed treatment-effect variation. Most participants, irrespective of selected treatment, felt their individual N-of-1 trials were helpful.


CONCLUSIONS
Implementation of the combined N-of-1 methodology is feasible in rheumatology practices and results confirm greater fibromyalgia improvement with combination therapy. This research approach broadens participation, although our trials' specifics likely influenced enrollment eligibility. In addition to individual benefits, combining N-of-1 trial data provides population research benefits. This patient-focused approach should be further explored to bridge research and practice.
Zucker
Deborah R
DR
Tufts University School of Medicine and Tufts-New England Medical Center, Boston, Massachusetts 02111, USA. dzucker@tufts-nemc.org
Ruthazer
Robin
R
Schmid
Christopher H
CH
Feuer
Jacqueline M
JM
Fischer
Peter A
PA
Kieval
Raphael I
RI
Mogavero
Nicola
N
Rapoport
Ronald J
RJ
Selker
Harry P
HP
Stotsky
Sharon A
SA
Winston
Eileen
E
Goldenberg
Don L
DL
D000328:Adult; D000639:Amitriptyline / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005356:Fibromyalgia / Q000188:drug therapy*; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010818:Practice Patterns, Physicians'; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012107:Research Design; D012219:Rheumatology / Q000639:trends; D018434:Sickness Impact Profile; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000928:Antidepressive Agents; D005473:Fluoxetine; D000639:Amitriptyline