The high-volume haemodiafiltration vs high-flux haemodialysis registry trial (H4RT): a multi-centre, unblinded, randomised, parallel-group, superiority study to compare the effectiveness and cost-effectiveness of high-volume haemodiafiltration and high-flux haemodialysis in people with kidney failure on maintenance dialysis using linkage to routine healthcare databases for outcomes.

Background: More than a third of the 65,000 people living with kidney failure in the UK attend a dialysis unit 2-5 times a week to have their blood cleaned for 3-5 h. In haemodialysis (HD), toxins are removed by diffusion, which can be enhanced using a high-flux dialyser. This can be augmented with convection, as occurs in haemodiafiltration (HDF), and improved outcomes have been reported in people who are able to achieve high volumes of convection.

Commentary: considerations for using the 'Trials within Cohorts' design in a clinical trial of an investigational medicinal product.

Background: The 'trials within cohorts' (TwiC) design is a pragmatic approach to randomised trials in which trial participants are randomly selected from an existing cohort. The design has multiple potential benefits, including the option of conducting multiple trials within the same cohort.

Main Text: To date, the TwiC design methodology been used in numerous clinical settings but has never been applied to a clinical trial of an investigational medicinal product (CTIMP).