Results Summary
What was the project about?
N-of-1 studies are studies that have only one patient. This type of study can help find the best ways to treat patients with long-term, or chronic, health problems, who may respond differently to the same treatment. Although N-of-1 studies show promise, researchers rarely use them.
In this project, the research team wanted to learn how N-of-1 studies worked to compare treatments for two chronic health problems. They also wanted to learn about patients’ experiences taking part in N-of-1 studies.
What did the research team do?
In the first study, the research team compared the effects of different diets in 54 children with inflammatory bowel disease, or IBD. Children started on their usual diet for two weeks. The team then assigned children by chance to either a specific carbohydrate diet, or SCD, or a modified SCD. Children alternated between the SCD and modified SCD diets every eight weeks for eight months.
In the second study, the research team examined how tracking triggers for a heart condition called atrial fibrillation, or AF, improved patients’ health. They enrolled 466 adults and assigned them by chance to one of two groups. One group looked at triggers that patients identified, like stress or caffeine. They tested whether changing those triggers improved patients’ AF. The other group only tracked patients’ symptoms. Patients in both groups recorded their data for 10 weeks.
Patients used a mobile app to record data in both studies.
To understand patients’ experiences, the research team interviewed 33 patients who completed the study.
Patients, parents of children with IBD, AF patient advocates, and doctors helped design the study.
What were the results?
Of the IBD patients, 39 percent completed the entire N-of-1 trial. The SCD and modified SCD worked similarly for most children. Compared with children’s usual diet, SCD and MSCD reduced symptoms and inflammation for some children.
Of the AF patients, 72 percent completed all study activities. Patients who tracked triggers had fewer AF episodes in the last four weeks of the study compared with patients who didn’t track their triggers. AF symptom severity was similar between the two groups.
Parents of children with IBD completed 63 percent of the daily symptom questions. Patients with AF completed 51 percent of daily symptom questions. Patients in the N-of-1 studies said they enjoyed learning from their data and testing behavior changes that might make them feel better. Some patients found it hard to follow treatment protocols and shift between treatments.
What were the limits of the project?
Many patients dropped out of the studies. The research team didn’t fully understand whether patients’ experience with the N-of-1 trial approach was part of the reason they decided to leave the studies early. Results may have differed if more patients had completed the studies.
Future research could look at ways to help patients complete N-of-1 studies.
How can people use the results?
Researchers can use these results when designing N-of-1 studies for patients with chronic health problems.
| How this project fits under PCORI’s Research Priorities The ImproveCareNow (ICN) network and the Health eHeart (HeH) Alliance were formerly Network Partners in PCORnet®, the National Patient-Centered Clinical Research Network. PCORnet® has been developed with funding from the Patient-Centered Outcomes Research Institute (PCORI®). |
Professional Abstract
Background
N-of-1 trials include one patient and compare the patient’s response to different treatments across different periods of time. This design can generate personalized data to help tailor treatments for individual patients. Although promising, researchers rarely use N-of-1 trials. More information about N-of-1 trials could support broader use.
Objective
To evaluate the feasibility, acceptability, and impact of N-of-1 trials to answer patient-identified research questions in two chronic conditions
Study Design
| Design Element | Description |
|---|---|
| Design | Series of N-of-1 trials; mixed-methods evaluation |
| Data Sources and Data Sets | Data from 2 research studies using N-of-1 designs that were conducted within 2 Patient-Powered Research Networks (PPRNs):
Interview data from a convenience sample of participants:
|
| Analytic Approach | Bayesian generalized linear modeling, analysis of covariance, descriptive analysis, thematic analysis of interview data |
| Outcomes |
|
Methods
Researchers used N-of-1 trial methods in two studies. They used a mobile app to provide instructions to patients and collect data.
In study 1, researchers compared the effectiveness of two diets—a specific carbohydrate diet (SCD) and a modified SCD (MSCD)—in reducing symptoms and inflammation among 54 children with inflammatory bowel disease (IBD). Participants first started on their usual diet for two weeks. Then, researchers randomly assigned participants to SCD or MSCD. Participants alternated between SCD and MSCD for a total of four treatment periods of eight weeks each.
In study 2, researchers randomly assigned 466 adult patients with atrial fibrillation (AF) to two groups. For six weeks, the trial group completed at least one N-of-1 trial where they alternated between one week of tracking triggers and one week of eliminating triggers, followed by four weeks of optional lifestyle changes informed by the N-of-1 results. The control group did not track or address trigger exposure over the same period. Researchers compared AF-related quality of life across groups.
Researchers interviewed a convenience sample of 33 participants in both studies regarding N-of-1 trial participation.
Patients with IBD, parents of children with IBD, AF patient advocates, clinicians, and researchers helped with the study design.
Results
Study 1. Among all participants, 39% completed the entire trial, 17% completed each treatment period once, and 44% withdrew prior to completing two full treatment periods. SCD and MSCD worked comparably for most individuals. Compared with the usual diet, SCD and MSCD reduced IBD symptoms and inflammation in some participants.
Study 2. Among 466 participants who initiated their randomized assignment, 72% completed all activities. Compared with the control group, the N-of-1 trial group experienced fewer AF episodes in the last four weeks of the trial. AF symptoms and severity were similar between the two groups.
Parents of study 1 participants entered data on 63% of daily symptom measures. In study 2, participants completed 51% of daily symptom measures. Participants appreciated learning from their data and having a personalized approach to managing their condition. Some participants had difficulty adhering to the N-of-1 trial protocols.
Limitations
Few people completed all N-of-1 trials in the series. Results may have differed if more people completed their full N-of-1 trial. The interviews may not have identified all the reasons for attrition.
Conclusions and Relevance
N-of-1 trials showed feasibility and acceptability in two different chronic conditions. Researchers can use these results when considering methods for studying treatments for chronic conditions that provide individuals with personalized results.
Future Research Needs
Future research could examine ways to promote retention during N-of-1 trials.
| How this project fits under PCORI’s Research Priorities The ImproveCareNow (ICN) network and the Health eHeart (HeH) Alliance were formerly Network Partners in PCORnet®, the National Patient-Centered Clinical Research Network. PCORnet® has been developed with funding from the Patient-Centered Outcomes Research Institute (PCORI®). |
Final Research Report
View this project's final research report.
Journal Citations
Results of This Project
Related Journal Citations
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- The reviewers pointed out that in the first study involving children with inflammatory bowel disease, “usual diet” was not a randomized intervention arm but more of a baseline condition; thus comparisons between usual diet and the other two diet interventions had some limitations. The researchers added a comment to their study limitations on this subject and changed their terminology in the paper from “usual diet” to “baseline diet.”
- The reviewers noted that less than half of the study participants fully completed the interventions, which the researchers partially dealt with by conducting separate analyses based on intervention completion. Given the apparent differences in the group of people who did complete the interventions fully, the reviewers asked the researchers to discuss how their analytic model differed from intention to treat principles and other limitations to the generalizability of the results. The researchers added additional pooled or aggregate analyses to the report that would be more in line with an intention-to-treat model. The researchers also commented that the N-of-1 study methods at the core of this research emphasizes individual differences that are important to understand effect heterogeneity rather than effect generalizability.
- The reviewers suggested that the researchers soften their very positive statements about the utility of N-of-1 study designs given the limitations the researchers faced in implementing these studies. The researchers also acknowledged that it was difficult to determine whether the challenges of the dietary interventions or the feasibility of N-of-1 trial designs was associated with their problems with participant recruitment and high drop out.
- Reviewers asked the researchers to add to their presentation of limitations for study 2 about individual-level triggers of atrial fibrillation, especially related to the high rate of missing data in this study. The researchers clarified that their analyses used complete cases and therefore could not be considered intention-to-treat.
- The reviewers asked why study 2 seemed to emphasize alcohol use as a potential trigger for atrial fibrillation. The researchers explained that alcohol use is currently the only potential trigger of atrial fibrillation with prior evidence in the literature and alcohol has some biological plausibility as a trigger.