N of 1 studies can make patient care more personalized

Randomized controlled trials (RCTs), the gold standard in clinical medicine, only tell us how the average patient responds to a treatment or an AI-based algorithm. N of 1 trials provide a unique opportunity to individualize patient care.

By John Halamka, M.D., president, Mayo Clinic Platform, and Paul Cerrato, senior research analyst and communications specialist, Mayo Clinic Platform

Large clinical trials are an important research tool that gives clinicians reliable guidelines on which treatments to use and which ones to abandon. But like most scientific advances, they have their shortcomings. A large trial may find that a specific medication or lifestyle regimen significantly reduces blood glucose among 4,000 people with Type 2 diabetes, for instance, giving medical practitioners confidence to prescribe it for their patients. Unfortunately, such trials can’t account for the heterogeneity of their patient panel, nor can they pinpoint which ones will be outliers who respond poorly, or with unexpected adverse effects. When faced with such unpredictable patients, physicians typically resort to trial and error, switching from one therapeutic approach to another until they find one that works. N of 1 studies offer an alternative to this hit or miss process.

During an N of 1 study, the treatment is usually given to a patient using a crossover design; in other words, a person is prescribed the active agent or a placebo without knowing which one they are taking. And at a certain point in the trial, they are switched to the opposite treatment. The blinding procedure eliminates the risk of patients responding because of their personal expectations. Of course, in order for these studies to remain ethical, clinician and patient must both agree to the protocol ahead of time.

Despite their advantages, n of 1 trials have their shortcomings too, and the U.S. Agency for Healthcare Research and Quality points out these limitations: “N-of-1 trials are applicable to chronic, stable, or slowly progressive conditions that are either symptomatic or for which a valid biomarker has been identified. Acute conditions offer no opportunity for multiple crossovers. Rapidly progressive conditions (or those prone to sudden, catastrophic outcomes such as stroke or death) are not amenable to the deliberate experimentation of n-of-1 trials.“ To date, the approach has proven helpful for patients with asthma, attention deficit hyperactivity disorder, fibromyalgia, and arthritis.

Although these types of one-on-one trials offer useful information that cannot be gleaned from RCTs, they are not without their obstacles, when compared to the more traditional trial and error approach to individualized therapy, including the need to meticulously collect patient data over time. There are digital tools that can help, including wireless patient monitoring. For example, it’s possible to track some effects of a medication in an individual patient with the help of a smartphone and the appropriate mobile app, including diaries to record adverse effects. Similarly, Lillie et al explain: “Such devices could be used to monitor activity levels of patients undergoing interventions for obesity and depression, or assess the tremor or mobility impairment of individuals with Parkinson’s disease. Activity monitors have become very sophisticated and could be used as adjuncts to other monitoring devices in an n-of-1 trial in which such monitoring may only be secondary to a primary set of measures.”

There really is no substitute for personalized patient care. Such care starts with a bond of trust between patient and clinician, and is then coupled with a physician’s knowledge of the most up to date medical research. But when the best clinical research doesn’t fit the needs of the patient that sits before you, it may be time to consider an n of 1 trial, if applicable.