TRAITS

We are recruiting patients from ICUs across Scotland. If you are or have recently been in an ICU in Scotland, or have a relative who has, then you may have been told about TRAITS. Not all ICU patients will be able to join TRAITS – the ICU doctors and nurses know who can take part, and they will speak to you or your relative if they think you, or they, are eligible to take part.

Critical illness is a challenge all over the world. In Scotland, approximately 11,000 patients each year develop a critical illness for which they need to be treated in ICU. Around 1 in 5 of them will die during their hospital stay, and around 2 in 5 will die within 60 days of their hospital stay. This is worse than for patients who were in hospital but not needing ICU intervention. We clearly need to improve this.

Clinicians, patient groups and research funders recognise that it is necessary to improve the situation for patients. The best way to do so is to run research studies to test how best to treat patients. There are many studies across the UK and the world doing just that.

TRAITS is also a study where clinicians are working together to find the best possible intervention for critically ill patients. But TRAITS is different to other critical care research studies, because we are trying to see if specifically matching the intervention to the patients is the best way to improve their outcomes. We call this type of medicine “precision medicine”.

Precision medicine is about giving the right intervention to the right patient at the right time. It is a powerful approach to treat and prevent disease. It uses various types of information about the patient (about their genes, their environment and lifestyle) to determine the best way to treat them.

Precision medicine is already used for some diseases, for example some types of cancers. It works like this:

• Clinicians test samples from these cancer patients, and look for particular indicators called biological markers or “biomarkers”. This is because they know from previous research that if the biomarkers are present, a certain intervention is more effective.
• Patients that have this biomarker can then receive the intervention that will work for them.
• These patients will have the best response to that intervention.

Patients who are admitted to ICU have life-threating illnesses, and doctors need to make immediate intervention decisions. This means it is not always possible to wait for test results to match interventions as is done for cancer patients like in the example above.

In TRAITS, we believe that we can apply precision medicine to critically ill patients if we first re-think how we identify the groups of patients who will respond to matched interventions. The way in which we do this in the TRAITS study is to group patients based on their clinical symptoms. We call each of these groups a “trait”. Each trait group is made up of patients whose bodies are fighting disease or injury in the same way. This means they have the same clinical symptoms, and they can receive the same interventions even though the reason that they are in ICU may be different.

The main benefit of grouping patients into traits in this way is that doctors and nurses in ICU can do it very quickly. This means that matched intervention can also be identified quickly.

We call this type of precision medicine Time Critical Precision Medicine (TCPM). TRAITS is the first TCPM in critical care, and is looking for patients from ICUs across Scotland.

TRAITS is a randomised controlled trial, testing multiple interventions (drugs) in multiple trait groups. It is an adaptive, platform trial. We will explain what all this means below.

A platform trial is different to a standard trial because we can test lots of different interventions at once in different groups, rather than just testing one intervention in one patient group. A platform trial also allows us to check the results as we go along, rather than waiting for the end of the study to see them.

An adaptive trial is a trial that we can change based on the data collected as we go along, instead of waiting until the end as is the case for most research studies. This means that in TRAITS, we can test lots of different interventions in each trait at the same time, and we can monitor how effective these interventions are as we go along. If the data shows that an intervention is not as effective as we thought, we can swap this for another intervention that we think might be better for patients.

The doctors and nurses in ICU will identify what patients can take part in TRAITS. If you, or your relative, might be eligible to take part, a doctor or nurse will speak to you about how it will work.

The TRAITS trial has 2 distinct but linked steps. You will need to give written consent (by signing a consent form) for both steps. Providing consent is essential and must happen before any other trial procedures as this ensures you understand what will happen to you, and that this will be different to what would happen if you were not taking part in the trial.

1. Step 1 is called the platform:
   • In the platform, we will look at the information in your or your relative’s medical notes (lab results, medical history and admission details) to decide if you fit into one of the trait groups. We will also ask you for a blood sample that we can use for research. This blood sample will be sent to research labs in the University of Edinburgh, and will help us discover more about the biology of critical care and hopefully improve interventions  for future patients.Your doctor or nurse will tell you if you fit into one of the trait groups. If you do, you will be eligible to take part in step 2.
2. Step 2 is called the Trait Specific Protocol (TSP):
   • In the TSP, you will be randomised to receive either a intervention (drug) in addition to usual care, or usual care only.  “Randomised” means you are allocated to the trial interventions (in this case either a drug and usual care or usual care only), by chance. In other words you or the doctor will not be able to decide what intervention you get.The doctor or nurse will tell you what you have been randomised to. We will collect data from your medical notes while you are in hospital and enter it in our trials database. We will regularly look at this data to see if the interventions  are working as we expect them to. At the end of the intervention, we will ask you for another blood sample that we can use for research. We will also send this sample to research labs in the University of Edinburgh, and compare it to the first sample; this will help us understand the biology of interventions given in the trial.