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Introducing N-of-1 trials to clinicians and researchers working with people who have a rare disease

N-of-1 Hub were delighted to design and deliver two webinars on N-of-1 trials earlier this year for the University of Ottawa. The request for a webinar came from researchers who are part of the INFORM RARE Network, a Canadian research network that is co-designed by patients and families, health care providers, policymakers, methodologists, and research ethicists. INFORM RARE’s mission is to work collaboratively to evaluate new and existing therapies and to make recommendations to improve care for children with rare genetic diseases. The webinars covered topics related to the design and analysis of N-of-1 trials in the context of rare disease. They were attended by clinicians and researchers from several fields including epidemiology, diagnostic radiology, clinical psychology, biochemical genetics, statistics and more.

What is the clinical problem?

A rare disease, often referred to as an orphan disease, is a medical condition that affects a relatively small number of people within a population. These conditions are characterised by their low prevalence, typically affecting fewer than 1 in 2000 individuals. Despite their individual rarity, collectively, rare diseases impact millions of people worldwide. Rare diseases can vary widely in terms of their symptoms, underlying causes, and prognoses. Clinical trials in rare diseases are crucial for developing effective treatments and improving the lives of affected individuals. Due to limited patient populations, these trials often require international collaboration and innovative trial designs.

What are N-of-1 trials?

N-of-1 trials use the patient as their own control to determine whether a treatment is effective for them. These study designs are often mistaken for “qualitative” or “descriptive” case studies, but they are prospectively designed quantitative studies that rigorously collect and analyse data from an individual. They are useful for studying conditions that affect small populations, where recruitment of sufficient numbers or patients for traditional clinical trials may be challenging. N-of-1 trials provide the opportunity for the highest level of evidence to be obtained about what works for an individual. Results can be used to inform shared decision-making about future management of a health condition.

Using N-of-1 trials in the field of rare disease

Dr Suzanne McDonald, Director of N-of-1 Hub, said: “N-of-1 trials are a perfect fit for evaluating treatments for rare disease. In contrast to traditional trials which focus on aggregated outcomes across groups of people, N-of-1 trials can be used to provide rigorous evidence about the effectiveness of interventions for an individual patient. This is because their design involves the patient acting as their own control. Furthermore, a series of N-of-1 trials can be combined to draw conclusions about treatment effectiveness for a larger group. Aggregated N-of-1 trials often require smaller numbers of participants than standard clinical trials because they involve collecting multiple outcome measurements per participant, which increases statistical power. Data from each N-of-1 trial can contribute to a cumulative evidence base until there is sufficient data to analyse as an aggregated N-of-1 trial.”

Dr Suzanne McDonald worked with Prof. James McGree, an expert in Bayesian statistics, to develop and deliver the two webinars. The first webinar described the basic principles of N-of-1 trial designs using illustrative examples, provided an overview of other single-case designs that can be valuable for studying rare diseases, and discussed key developments that have occurred in the field over the past decade. The second webinar provided an overview of common techniques used to evaluate data from individual and aggregated N-of-1 trials and discussed key topics including autocorrelation and sample size determination.

Attendee feedback indicated a keen desire for more learning opportunities in this space. An attendee said: “It was one of the best presentations...well organized, at appropriate level, and with enthusiasm that makes me want to learn more...extremely well done...thank you so much for introducing me to such an exciting area....”

N-of-1 Hub is a consulting company that specialises in designing, conducting and analysing personalised clinical studies using single-case designs. N-of-1 Hub also offers data management and analysis services and customised training workshops.

For further information about N-of-1 Hub, and to discuss your study needs, please contact us.

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