Effect of Mobile Device-Supported Single-Patient Multi-crossover Trials on Treatment of Chronic Musculoskeletal Pain: A Randomized Clinical Trial

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 participants: This 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 measures: The 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 relevance: In 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.

Figure 1.. Examples of Graphical Output Provided to Patients and Their Clinicians in the n-of-1 Arm During Results Review Visits

Patients and clinicians were provided with 6 graphs during the results review visit; 3 are depicted here. The graphs were intended to be devoid of jargon and easily understood and interpreted by patients and clinicians. Clinicians were provided access to brief web-based training videos to assist them in interpreting the graphs for their patients. The patient in this example compared acetaminophen as treatment A (shown in light blue) with a nonsteroidal anti-inflammatory drug as treatment B (shown in dark blue). The graphs in panels B and C depict 6 patient-centered outcomes (pain intensity, fatigue, drowsiness, sleep problems, thinking problems, and constipation) comparing treatment A with treatment B. A, The daily ratings on a 0- to 10-point scale for pain intensity, which were entered into the Trialist app by the patient. Zero indicates no pain, and 10 the highest level of pain. Each data point indicates 1 day. B, The average of daily ratings on a 0-10 scale for each outcome. Zero designates the best outcome. C, The outcomes are shown as squares representing point estimates for relative improvement, with lines representing the 95% credible intervals, and color shading and labeling to facilitate decision making. The analysis in this panel was based on a Bayesian model that estimated the posterior distribution of the difference between symptom scores comparing treatment A with treatment B.

Figure 2.. Enrollment Flowchart for Personalized Research for Monitoring Pain Treatment Study Patient Recruitment and Enrollment

Patients who no longer wished to continue in the study were classified as withdrew. Patients who could not be located were classified as lost to follow-up, while those missing data at a particular follow-up time point were classified as did not complete follow-up. Patients who had not completed the intervention before the 3-month window ended were classified as completed the results review visit after the follow-up window had closed. Patients enrolled at the end of the recruitment period and not followed beyond 6 months were classified as enrolled within 12 months of end of study.