Development of generalisable methodology for n-of-1 trials delivery for very low volume treatments (DIAMOND)

A study funded by the NIHR to develop a set of principles for n-of-1 trials and to provide guidance on how these trials should be conducted.

Logo of the DIAMOND research project


Patients can respond in different ways to the same treatment depending on factors such as their: age, co-morbidities, genetics and lifestyle. Therefore, when it comes to therapy, ‘one size fits all’ may be an inappropriate philosophy.

n-of-1 trials are a type of multi-period cross-over study in which the effects of a treatment or health technology are studied by following an individual patient over time with the treatments that are given randomised from period to period.

n-of-1 trials can be undertaken to evaluate health technologies both to treat an underlying medical condition as well as the symptoms of the condition; for example palliative pain management or antiemetic treatments. The trials can be used to assist in the personalisation of treatments for a given patient. They can also be used for different purposes such as increasing the study efficiency by replicating the treatments.

The NIHR commissioned this research to develop a methodology that underpins n-of-1 trials in order to ensure rigour and consistency in their use and to enable n-of-1 trials to be employed in as many rare disease areas and low-volume interventions/treatments as possible.


The aim of this research project was to develop a set of principles and a methodology template for n-of-1 trials and to provide guidance on how these trials should be conducted. Specific objectives were to 

  • review existing literature on n-of-1 trials

  • conduct stakeholder focus groups to gain an understanding of the types of question(s) that can be addressed with n-of-1 trials, the treatments that can be investigated and possible trial outcomes

  • generate a guidance document that makes clear when it is appropriate to undertake n-of-1 trials and what questions can be addressed

  • provide two training courses (one for statisticians, one for non-statisticians) to disseminate findings

  • produce a user-friendly guide to enable an analysis of n-of-1 trials in statistical packages SAS and R


A full report of the DIAMOND project, including a list of key points to consider when designing and undertaking n-of-1 trials, can be found here.

Resources to assist researchers in analysing data from n-of-1 trials can be downloaded by following the link below:

DIAMOND programs


This project has been funded by NIHR CTU Support Funding.


Please contact Liv Hawksworth (Research Assistant at Sheffield Clinical Trials Research Unit) at

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