Effect of Mobile Device–Supported Single-Patient Multi-crossover Trials on Treatment of Chronic Musculoskeletal Pain

Abstract

IMPORTANCE Individually designed single-patient multi-crossover (n-of-1) trials can facilitate tailoring of treatments directed at various conditions, including chronic musculoskeletal pain (CMSP) but are potentially burdensome, which may limit uptake in research and practice.OBJECTIVES To determine whether patients randomized to participate in an n-of-1 trial supported by a mobile health (mHealth) app would experience less pain and improved global health, adherence, satisfaction, and shared decision making compared with patients assigned to usual care. DESIGN, SETTING, AND PARTICIPANTSThis randomized clinical trial compared participation in an individualized, mHealth-supported n-of-1 trial vs usual care. The participating 215 patients had CMSP for at least 6 weeks, had a smartphone or tablet with a data plan, were enrolled in northern California from July 2014 through July 2016, and were followed for up to 1 year by 48 clinicians in academic, community, Veterans Affairs, and military settings.INTERVENTIONS Intervention patients met with their clinicians and used a desktop interface to select treatments and trial parameters for an n-of-1 trial comparing 2 pain-management regimens. The mHealth app provided reminders to take designated treatments on assigned days and to upload responses to daily questions on pain and treatment-associated adverse effects. Control patients received care as usual. MAIN OUTCOMES AND MEASURESThe primary outcome was change in the PROMIS (Patient-Reported Outcomes Measurement Information System) pain-related interference 8-item short-form scale (full scale range, 41-78) from baseline to 6 months. Secondary outcomes included patient-reported pain intensity, overall health, analgesic adherence, trust in clinician, satisfaction with care, medication-related shared decision making, and, for the n-of-1 group only, participant engagement and experience. RESULTS Among 215 patients (108 randomized to the n-of-1 intervention and 107 to control), 102 (47%) were women, and the mean (SD) age was 55.5 (11.1) years. At the 6-month follow-up, pain interference was reduced in both groups, though there was no difference between the intervention and control groups (−1.36 points; 95% CI, −2.91 to 0.19 points; P = .09). There were no advantages in secondary outcomes for intervention patients vs control patients except for higher medication-related shared decision making at 6 months (between-group difference, 11.9 points; 95% CI, 2.6-21.2 points; P = .01). Among patients assigned to the n-of-1 group, 88% (n = 86) affirmed that the mHealth app could help people like them manage their pain. CONCLUSIONS AND RELEVANCEIn this population of patients with CMSP, mHealth-supported n-of-1 trials were feasible and associated with a satisfactory user experience, but n-of-1 trial participation did not significantly improve pain interference at 6 months vs usual care.TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02116621

Application of n-of-1 Clinical Trials in Personalized Nutrition Research: A Trial Protocol for Westlake N-of-1 Trials for Macronutrient Intake (WE-MACNUTR)

“…It can capture intraindividual variability in health behaviors over time, aiming to identify individual responses to a given intervention in a controlled trial, which provides a great opportunity to assess the personalization potential of different diets, nutrients, or nutrition supplements ( 16 – 18 ). The idea of n -of-1 has been applied in special education, psychotherapy, psychology, and pharmaceutical studies for decades to test the individual response to specific drugs or treatments ( 19 – 23 ). A previous study reported the efficacy of mexiletine on reducing muscle stiffness in patients with nondystrophic myotonia using a series of n -of-1 trials ( 24 ).…”

Measuring the Effects of Caffeine and L-Theanine on Cognitive Performance: A Protocol for Self-Directed, Mobile N-of-1 Studies

“…The success of this clinical implementation is dependent on the study design (what is being compared), and the willingness and collaboration of the patient, and the capacity of the clinician to design and implement an n-of-1 trial. With more than 2000 of these trials published to date, examples of previous implementations include an appbased study of the treatment of chronic musculoskeletal pain (Kravitz et al, 2018;Odineal et al, 2019), as well as stimulant effectiveness among people with attention deficit/hyperactivity disorder (Nikles et al, 2006).…”

Application of n-of-1 clinical trials in personalized nutrition research: a trial protocol for Westlake N-of-1 Trials for Macronutrient Intake (WE-MACNUTR)

“…It can capture intra-individual variability in health behaviors over time, aiming to identify individual response to a given intervention in a controlled trial, which provides great opportunity to answer the personalization potential of different diets, nutrients or nutrition supplements [16][17][18] . The idea of n-of-1 has been applied in special education, psychotherapy, psychology and pharmaceutical studies for decades to test the individual response to specific drugs or treatments [19][20][21][22][23] . Stunnenberg et al reported the efficacy of mexiletine on reducing muscle stiffness in patients with nondystrophic myotonia (NDM) using a series of nof-1 trials 24 .…”