'25 at 25': The PRACTical trial design

15 Feb 2024

As part of the MRC Clinical Trials Unit at UCL’s 25th anniversary celebrations, we highlight the Unit’s role in developing new clinical trial designs to address problems where standard trial designs are not sufficient. This article focuses on the ‘Personalised RAndomised Controlled Trial’ (PRACTical) trial design. It is part of a series highlighting 25 major achievements from the 25 years since the MRC CTU at UCL was formed.

The PRACTical design allows researchers to compare multiple treatments for diseases that don’t have a single “standard-of-care” treatment that every patient could take. In certain clinical areas such as multi-drug resistant infections, multiple treatments are potentially useful, but they may not all be appropriate for every patient. For example, one of the available antibiotics might be unsuitable for patients with additional medical conditions or for patients with infections that are already resistant to that type of antibiotic. These people would normally be excluded from a traditional trial, meaning that doctors have little evidence on how best to treat them.

The PRACTical design tackles this problem by randomising patients only among treatments that are suitable for them. PRACTical trials produce a ranked list of treatments, which clinicians can use to help decide which treatments are likely to perform best for each patient.

List of treatments A to J with some crossed out with a line through. Those that are not crossed out have an arrow coming from the text, pointing to a hand flipping a coin.
In a PRACTical trial, participants are randomised only among treatments that are suitable for them. Any treatments which a particular patient cannot take are ruled out before randomisation.

We are developing methodology which underpins the design, analysis and implementation of these trials. We also provide guidance on how to use the PRACTical design, including statistical methods for evaluating the design and determining sample size.

We are currently designing new PRACTical trials in the areas of snakebite and multi-drug resistant typhoid. We have already used the PRACTical design in our NeoSep1 trial, which compares multiple antibiotic regimens for treating sepsis in newborn babies.

The PRACTical design is particularly useful for addressing the problem of neonatal sepsis as there are many antibiotic regimens currently used around the world, but little evidence to guide clinicians on which to use for newborn babies. There are also different patterns of antimicrobial resistance in different parts of the world, so what works well in one setting may not work well elsewhere. Some babies may also be unable to take specific medicines due to side-effects. NeoSep1 will enable clinicians to choose treatment regimens that are likely to work well, depending on the setting and characteristics of the baby.

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