Sheffield CTRU Randomisation System

In the past we've kept our randomisation lists and/or randomisation envelopes on site and used them ourselves. Why do we need this extra service?

There are three key reasons why our system can improve randomised trials:

• Security - Our system holds the randomisation list on a password-restricted access server, and its content is maintained and backed up every day.
• Accessibility - Our system is available 24 hours a day throughout the year.
• Management - The maintaining of a paper-based randomisation system is an overhead that should not be underestimated. Our system reduces this burden greatly, allowing you to concentrate on more interesting things.

Does good clinical practice (GCP) impact on our choice of randomisation system?

For your trial's randomisation system to comply with GCP, it will need to retain an audit trail. The documentation required by this includes the date, time and patient details for each randomisation. Whilst this can be done using a paper-based system, there are three main drawbacks to doing so: effort, accuracy, and authentication. When the necessary details are not recorded (or misrecorded) at the point of randomisation, it can be difficult if not impossible to recover this information; moreover, it is harder to maintain and monitor this system and harder to detect fraudulent use.

The CTRU randomisation system automatically records the activities on each log-in. This meets the GCP requirements and, unlike paper-based systems, provides an authenticated date/time stamp. It also removes the need for additional paperwork and hence saves time, space and ultimately money.

Can't we get away without being GCP compliant?

If your trial is using an investigational medicinal product or medical device, then GCP compliance is a legal requirement. In other cases, GCP is a recommendation. General regulatory guidance stops short of insisting on a central electronic approach but does recommend its use, especially where the trial is single-blind, open-label or multi-centre*.

How is the system set up and maintained?

The CTRU randomisation system is a web-based package. We can provide training from which you can set-up and manage the system yourself, or we can do it for you. We provide full system back-up and maintenance.

Who gets to use the system and how do they do it?

All users need is a computer with a web browser and internet connection to access the system - nothing else. The randomisation system will typically be used by several members of the trial team, including the trial manager, statistician, independent reviewers and those who use it to randomise patients. The web system recognises these different types of users and allows the relevant level of access.

What detail does the user see?

The level of detail viewable is tailored to the needs of the user. A study manager will be able to view trial progress, whereas investigators using the system solely to randomise patients will not. Similarly, the randomisation list itself can be restricted to authorised users, such as independent members.

So the system will help me keep track on the study progress?

Our system also allows you to proactively monitor your trial. Study managers can get real-time details of how many subjects are being randomised by site, and so can keep track of when extra supplies are needed by pharmacy, for instance. As any study manager who has done this in the past will confirm, this is a very useful tool to have!

What does the randomisation system look like?

Patients are randomised by a secure link to a central randomisation database. Randomisation is done via a web-interface in which the user can be allowed to remain blind to treatment. Additionally, we can randomise patients via automated telephone link if you prefer. Both options are available 24 hours a day.

And access to the randomisation codes can be controlled?

In double blind studies, access to the treatment codes is restricted (typically to pharmacy staff and independent monitors), whilst in single-blind or open-label trials the treatment can be revealed as soon as the patient's details have been registered with the system. The system allows you to do either. There is also a 24 hour access code break which can be used in emergency to identify any individual patient's treatment. The system automatically logs this information and informs the principal investigator straightaway.

How do I tailor it to our trial's requirements?

For access to the system, you name the individual users and decide what level of detail they need to see. For the randomisation list, you decide what it should look like: our system is customised to ensure the number of patients, stratifying factors, block size and many other aspects are as you want them. The CTRU can offer our advice on these choices if you need it.

How do I find out more?

Email us on ctru@sheffield.ac.uk

* International conference on harmonisation (ICH) of technical requirements for registration of pharmaceuticals for human use: Topic E9, "Statistical principles for clinical trials" (1998). Section 2.3.1 states "In multicentre trials the randomisation procedures should be organised centrally" and "For [single-blind and open-label] trials, consideration should be given to the use of a centralised randomisation method".