N-of-1 Trials: Evidence-Based Clinical Care or Medical Research that Requires IRB Approval? A Practical Flowchart Based on an Ethical Framework

Abstract

N-of-1 trials can provide high-class evidence on drug treatment effectiveness at the individual patient level and have been given renewed interest over the past decade due to improvements of the initial single patient design. Despite these recent developments, there is still no consensus under what circumstances N-of-1 trials should be considered as part of evidence-based clinical care and when they represent medical research with need for institutional review board (IRB) approval. This lack of consensus forms an obstacle for a more widespread implementation of N-of-1 trials. Based upon the existing literature, we as a group of researchers involved in N-of-1 trials and members of the IRB of a tertiary academic referral center, designed a practical flowchart based on an ethical framework to help make this distinction. The ethical framework together with a practical flowchart are presented in this communication.

Optimizing clinical research procedures in public health emergencies

“…Due to limited experience, regulatory and ethical bodies are less familiar with this design which may hinder progress, although work has been done to try an establish a clearer framework for designing and conducting N‐of‐1 studies 29–32 . In the context of a Public Health Emergency, small data approaches may provide value in discovering novel therapeutics incorporated into master protocol designs, although this does not appear to have been formally documented during prior pandemics.…”

N-of-1 Trials in Healthcare

“…In addition to these barriers, there is often uncertainty about whether N-of-1 trials and single-case studies require ethical approval from an institutional review board, which stems from the debate about whether single-case designs are medical research or clinical care. In this Special Issue, Stunnenberg et al [ 13 ] present a practical flowchart based on an ethical framework aiming to support decision-making about the requirement for ethics approval.…”

Improving research ethics review and governance can improve human health

“…To guide when n-of-1 trials should require ethics review, a group has developed a simple flowchart, 14 but we are not aware of jurisdictions currently using this.…”