Trial Design
The PITHIA trial has two relatively novel elements of trial design: firstly, it is a registry-based, randomised clinical trial. Secondly, it is has a ‘stepped-wedge cluster’ design. These elements should help keep the costs of the trial to a minimum, just a fraction of the costs of a typical national, multi-centre trial. In addition, the trial design aims to minimise the time and effort required by busy clinicians and patients.
Trial Design
The PITHIA trial will be testing whether transplant centres increase the number of kidneys they transplant, and how well those kidneys work, after the introduction of the national histopathology service. The full trial protocol is available here: PITHIA Protocol v2.0
Figure 1a: Control arm – flow diagram describing current practice
Figure 1b: ‘Treatment’ arm. Flow diagram describing process following ‘switch-over’.
Stepped-wedge cluster randomised trial
The PITHIA trial is a stepped-wedge cluster trial which is a design that has some particular advantages for this type of study. The cluster design (in which randomisation happens at the level of the transplant centre, rather than individual patient) is planned to prevent ‘contamination’ across the ‘control’ and ‘experimental’ groups. This means that as centres change their behaviour as the histopathology service begins, this will be limited to those centres which have been selected to receive the service, so that we can interpret what the effect of the service has been.The standard ‘parallel cluster design’ selects half of the centres at random to receive the intervention (in this case, histopathology). However, for an intervention that has the broad support of the majority of transplant clinicians, the ‘stepped-wedge’ cluster design allows the treatment to be rolled out to every centre. The randomisation controls when centres will recieve the service, in a ‘stepped’ fashion, enabling us to compare results at each centre, before and after the introduction of the urgent histopathology service.
Randomised Registry Trial
Transplantation is very fortunate that in order to regulate and administer the national transplant service we have a large UK-based transplant registry which stores information about donors, recipients and transplants. This is used to ensure that organs are allocated appropriately, and that the quality of transplants are monitored. This registry-randomised trial will use the data that is already routinely collected as part of the registry. This aims to reduce the costs of running the trial dramatically, as well as reducing the burden of taking part, for both patients and clinicians. Read about randomised registry trials here.
