N-of-1 Trials and Their Role in Improved Healthcare Outcomes
N-of-1 trials represent an individualised approach to healthcare treatment, designed specifically for a patient with a rare disease to facilitate personalised healthcare approaches.
Typically conducted in patients with chronic diseases, N-of-1 trials see individual patients given candidate treatments in double-blinded, random sequences of alternating periods to determine the most effective treatment for that patient.
For patients with chronic conditions such as asthma, heart failure, or fibromyalgia, doctors and clinicians will often prescribe a medication for an initial period to learn how well it works for that patient and to inform a decision about a longer-term treatment.
However, it can be difficult to apply the results of a conventional study or a randomised controlled trial to an individual patient (regardless of any clinical guidelines to shape treatment).
A patient may not have met the eligibility requirements from the original trial, or random clinical trial data may not be available for certain rare diseases.
N-of-1 trials aim to provide an alternative approach which is more patient-centric, reinforcing shared decisionmaking between a patient and their doctor or GP around treatments.
How N-of-1 Trials Work
Although N-of-1 trials have been explored by clinical researchers for over three decades, they have seen limited implementation to date.
Patients are given candidate treatments – which may include placebos – over a structured time period with regular checkups and data collection.
Treatments are provided in a randomised order, and are double-blinded: neither the patient nor their doctor knows which treatment is being given in a certain period.
By supporting personalised, evidence-based decision making as part of a patient’s usual healthcare routine, N-of-1 trials are effectiveness trials – as opposed to efficacy trials, which test treatments in ideal subjects under optimised conditions.
Since they typically compare alternative treatments, N-of-1 trials can be considered as comparative effectiveness trials which are tailored to the care of a single patient.
N-of-1 trials are most commonly used for chronic conditions with relatively slow rates of progression: the sequential approach is generally not suited to rapidly progressive conditions, as the changeable underlying trajectory may undermine treatment comparisons.
For patients with fibromyalgia, relevant outcomes include a reduction in pain and an improvement in sleep patterns; for patients with heart failure, biomarker strategies may represent the best approach for monitoring outcomes.
Across these diseases, N-of-1 trials yield results specific to individual patients and enhance the comparisons of treatments, with the patients themselves serving as their own controls.
Constraints in Implementation
While N-of-1 trials have a lot of potential utility in developing treatment outcomes for patients with chronic diseases, the standard infrastructure required for their broader implementation and uptake does not currently exist.
To date, these trials have rarely been conducted outside of research settings, and have not been integrated into general care.
In order for their potential for producing clinical and research benefits to be fully realised, N-of-1 trials will have to fit into the current healthcare ecosystem.
Collaborative conduct between researchers, hospitals, and academic institutions could provide the pathway to broader trial availability.
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