Patients and primary care providers identify opportunities for personalized (N-of-1) trials in the mobile health era.

N-of-1 trials are multiple crossover design experiments in which individual patients compare two or more treatments to one another.¹ Given their potential to generate strong evidence for personalized treatment selection, N-of-1 trials generated tremendous excitement in the 1980s.^2–4 Despite early promise, efforts to implement N-of-1 trials have faltered.⁵ In the last decade, however, enthusiasm for precision medicine and mobile health technology have created new opportunities for N-of-1 trials. Accordingly, we conducted focus groups with patients and primary care providers to examine perceived benefits and limitations of employing N-of-1 trials.

Between April and September of 2016, we recruited 54 English and Spanish speaking patients in New York City (NYC) from primary care clinics affiliated with New York-Presbyterian Hospital and nationally, from the COPD Foundation. Twenty-four primary care providers were recruited from NYC clinics. Participants were provided with a description of N-of-1 trials and were asked about their attitudes toward N-of-1 trials. Thematic content analysis identified emergent themes. All participants provided informed consent, and the study was approved by the Institutional Review Board of Columbia University Medical Center.

We found that patients (mean age 62 years, 43% women) and clinicians (mean age 37 years, 61% women) readily understood the benefits N-of-1 trials (Table), including the potential to individualize treatment selection, with one patient explaining “because it individualizes what’s good for you, not for the percentage of the masses.” Additional benefits included opportunities for patient engagement in self-care, better patient-doctor communication, and ultimately, improved patient outcomes. Patients also appreciated the opportunity to engage in the research enterprise. Clinicians recognized the potential to gain generalizable knowledge from pooled N-of-1 results.

Table.

Perceived Benefits of N-of-1 Trials by Primary Care Providers and Patients

Providers, only	Providers and patients	Patients, only
Increases patient adherence to treatment	Improves patient outcomes by identifying evidence-based treatments for individual patients	Provides opportunity to participate in research
Improves clinical management through better understanding of patient experience	Improves patient-clinician relationship and satisfaction with care by making patients feel like they are being treated as unique
	Increases patient engagement in care
	Improves patient understanding of health condition and treatment effects

Patients and clinicians also identified barriers. Most notably, the time burden, responsibility, intrusiveness, and cost of participation were mentioned. Further, both groups expressed concern that N-of-1 trials could disrupt the patient-clinician relationship by making some patients feel like “guinea pigs”. Some also expressed concerns that N-of-1 trials could intrude upon the time available for routine clinical care and could delay treatment decisions. Clinicians additionally highlighted regulatory demands and start-up costs.

For N-of-1 design features, there was high acceptability of mobile health technologies. Patients and providers recognized that mobile health could substantially lower the burden of conducting N-of-1 trials, particularly if integrated into the electronic health record. Patients and providers were generally accepting of patient but not clinician blinding, given concerns for safety. While clinicians were enthusiastic about comparing active treatment with placebo to clarify treatment effects, patients generally disliked placebo comparisons. Patients and providers differed in their preferences for clinician involvement: patients preferred close involvement by their treating providers whereas clinicians preferred that trials be conducted through an N-of-1 service.

Our findings suggest that advances in mobile health and personalized medicine are fostering favorable attitudes toward N-of-1 trials, thus creating a new context for them to succeed. Concerns about N-of-1 trials related to cost and burden can potentially be overcome through scalable, user-friendly apps that facilitate unobtrusive monitoring using mobile health devices. Trials to determine the feasibility and effectiveness of mobile health-enabled N-of-1 trials are now warranted.⁶

Highlights.

• N-of-1 trials can be used to help patients compare the effectiveness of treatments.

• Patients and providers identified multiple potential benefits of N-of-1 trials.

• Key benefits were personalized treatment selection and enhanced patient engagement.

• Key concerns included time and resource burden and disruption of routine care.

• There was high acceptability of using mobile health to facilitate N-of-1 trials.