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.
RCT Entities:
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.
Authors: David D Odineal; Maria T Marois; Deborah Ward; Christopher H Schmid; Rima Cabrera; Ida Sim; Youdan Wang; Barth Wilsey; Naihua Duan; Stephen G Henry; Richard L Kravitz Journal: J Gen Intern Med Date: 2019-08-28 Impact factor: 5.128
Authors: Richard L Kravitz; Christopher H Schmid; Maria Marois; Barth Wilsey; Deborah Ward; Ron D Hays; Naihua Duan; Youdan Wang; Scott MacDonald; Anthony Jerant; Joseph L Servadio; David Haddad; Ida Sim Journal: JAMA Intern Med Date: 2018-10-01 Impact factor: 21.873
Authors: Parag Goyal; Monika M Safford; Sarah N Hilmer; Michael A Steinman; Daniel D Matlock; Mathew S Maurer; Mark S Lachs; Ian M Kronish Journal: Br J Clin Pharmacol Date: 2022-07-13 Impact factor: 3.716
Authors: Jennifer S Gewandter; Michael P McDermott; Hua He; Shan Gao; Xueya Cai; John T Farrar; Nathaniel P Katz; John D Markman; Stephen Senn; Dennis C Turk; Robert H Dworkin Journal: Clin Pharmacol Ther Date: 2019-03-12 Impact factor: 6.875