In 1985, a group of Canadian clinical investigators’ interest was piqued by a 65-year-old asthmatic male whose symptoms had been poorly managed using two drugs, Theophylline and Ipratropium bromide, that were normally successful in other patients.

They designed a blinded trial to test the utility of the Theophylline in this patient, which involved alternating paired treatment blocks of Theophylline and a placebo, or Ipratropium bromide and a placebo. After just four blocks of treatment, the results clearly showed that the patient’s symptoms worsened when treated with Theophylline.

Randomised controlled trials (RCTs) are the keystone of evidence-based medicine, but they can only provide data on how well a treatment works on average for the subjects in a trial. They can never predict how well any individual will respond. In the case of this particular asthma sufferer, he would have appeared as an anomaly in a large RCT.

N-of-1 trials are designed to rigorously test the effectiveness and safety of a treatment on a single patient by randomising treatments ‘within’ the individual. They are used when an individual patient has unique characteristics that raise questions about the suitability of conventional treatments. For example, patients with comorbidities or complex medical conditions, rare diseases, or sub-groups of patients who may be resistant to usual drug treatment due to individual factors or genetic abnormalities.

ISCRR undertook an Evidence Review of the utility and methodology of N-of-1 trials. From a review of 89 articles, the research team documented the models that currently exist for N-of-1 studies and the essential criteria necessary to proceed.

The main benefits of an N-of-1 trial are the patient-centred focus, the direct benefits to the patient, and the enhanced communication between the patient and provider. N-of-1 trial design brings the most value to a patient-centred care approach when there is uncertainty related to:

  1. the comparative effectiveness of treatment options (e.g. mixed results from RCTs)
  2. the absence of good quality clinical trials (e.g. rare conditions)
  3. the effectiveness of new therapies that demonstrate marginal benefits compared with existing treatments
  4. the individual patient’s unique characteristics that differ substantially from existing clinical trial participants

The biggest challenge to the N-of-1 approach is that it takes time and effort from both patient and health care provider. Ultimately, the rigour of the N-of-1 model may reduce the time wasted on ineffective treatments and identify a clearer path to recovery.