top of page
Writer's pictureICN

N-of-1 Trials: A Scientific Approach to Personalised Medicine for Patients with Rare Retinal Disease

Authors: Zarbin & Novack (2021)


This article focuses on Retinitis Pigmentosa (RP), a group of inherited retinal degenerative diseases with a prevalence of ∼1 in 4,000, affecting 2 million persons globally. There are >50 ongoing retinal gene therapy clinical trials, most of them for relatively rare diseases such as RP. There are two fundamental problems associated with assessing treatments for RP; small target patient populations and patient heterogeneity, which mean the traditional parallel randomised controlled trial (RCT) design may not be feasible. Alternative methodologies include cross-over designs, adaptive designs (including response-adaptive randomisation, ranking and selection, internal pilot, sequential designs), and N-of-1 trials. N-of-1 trials are randomised, prospective, controlled, multiple crossover trials in a single patient. According to the Oxford Centre for Evidence-Based Practice, aggregated N-of-1 trials constitute level 1 evidence (as do systematic reviews of randomised trials). Advantages of N-of-1 trials summarised in the article include that each patient is assured exposure to the experimental treatment, which may facilitate recruitment. In addition, each patient serves as his/her own control, which reduces variance, minimises confounding and enables recruitment of patients with comorbidities, which is generally discouraged in parallel group RCTs. As a result, it may be easier to identify treatment effects, or lack thereof, in specific subpopulations of patients. Limitations of N-of-1 trials are also discussed, such as the potential for drop out (although this is also a concern in group-based RCTs) and carryover effects. Despite the limitations identified, the authors explain how N-of-1 trials can provide a useful means by which to assess treatments for rare diseases with rigor equal to or greater than that afforded by parallel group RCTs. N-of-1 trials can be considered as alternatives to parallel group RCTs when the number of potential participants is small because of the rarity of the underlying condition.


Click here to read the article.


Full reference: Zarbin, M. A., & Novack, G. (2021). N-of-1 Clinical Trials: A Scientific Approach to Personalized Medicine for Patients with Rare Retinal Diseases Such as Retinitis Pigmentosa. Journal of Ocular Pharmacology and Therapeutics, 37(9), 495-501.

146 views0 comments

Comments


bottom of page