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Lessons Learned Combining N-of-1 Trials to Assess Fibromyalgia Therapies
DEBORAH R. ZUCKER, ROBIN RUTHAZER, CHRISTOPHER H. SCHMID, JACQUELINE M. FEUER, PETER A. FISCHER, RAPHAEL I. KIEVAL, NICOLA MOGAVERO, RONALD J. RAPOPORT, HARRY P. SELKER, SHARON A. STOTSKY, EILEEN WINSTON, and DON L. GOLDENBERG ABSTRACT. 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. Conclusion. 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. (J Rheumatol 2006;33:2069-77) Key Indexing Terms:
N-of-1 From the Tufts University School of Medicine and Tufts–New England Medical Center, Boston; and Newton-Wellesley Hospital, Newton, Massachusetts, USA. Supported by grant RO1 AR45416 (Principal Investigator: Dr. Zucker) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The sponsor did not participate in the design and conduct of this study, in the collection, analysis and interpretation of the data, or in the preparation, review or approval of this report. D.R. Zucker, MD, PhD; R. Ruthazer, MPH; C.H. Schmid, PhD; H.P. Selker, MD, MSPH, Tufts University School of Medicine and Tufts-New England Medical Center; J.M. Feuer, MD, Private Practice; P.A. Fischer, MD, Private Practice and Sturdy Memorial Hospital; R.I. Kieval, MD, Private Practice; N. Mogavero, MD, Private Practice; R.J. Rapoport, MD, Private Practice; S.A. Stotsky, MD, Private Practice; E. Winston, MD, Private Practice; D.L. Goldenberg, MD, Newton-Wellesley Hospital. Address reprint requests to Dr. D.R. Zucker, Tufts-New England Medical Center, NEMC Box 63, 750 Washington Street, Boston, MA 02111, USA. E-mail: dzucker@tufts-nemc.org Accepted for publication May 1, 2006.
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