LAVA: Liver Resection Surgery Versus Thermal Ablation for Colorectal Liver Metastases
Description: A multi-centre trial comparing the effectiveness and cost-effectiveness of thermal ablation versus liver resection surgery in high risk patients eligible for liver resection. Due to the number of UK sites that could perform both thermal ablation and liver resection and the anticipated small number of patients who would be suitable for the trial, international recruitment was thought to be essential to reach the required number of patients in a realistic timescale.
It was planned that 15 UK sites and 5 sites from the Netherlands would take part in the trial, with one site in the Netherlands taking the role as local spoke.
Countries: United Kingdom and the Netherlands
University College London (UCL) acted as sponsor for the trial, with co-ordination of the trial delegated to the Clinical Trials Research Unit at the University of Leeds. A lead site was identified in the Netherlands to apply for national ethical approval and assist with local site set-up.
University College London (UCL) obtained funding for the trial as the host organisation. This included payments to facilitate delivery of the research at both UK and Dutch sites.
University College London contracted with each participating research site in the UK and in the Netherlands. The sponsor delegation of duties to the Clinical Trials Research Unit at the University of Leeds was covered in a separate agreement.
A local insurance policy was required for sites in the Netherlands, which was taken out by the lead site in the Netherlands and subsequently reimbursed by the sponsor, University College London. International sites were responsible for ensuring appropriate insurance or indemnity for clinical negligence was in place in their respective country and in relation to their clinical activities related to the trial.
The lead site in the Netherlands was responsible to obtaining national ethical approval, local board approval was then obtained by each Dutch site. Evidence of local approvals were collected prior to the site being opened to recruitment. International sites were responsible for local safety reporting as per local regulations.
Separate protocols were developed for the UK and the Netherlands to reflect local processes. The Dutch version of the protocol was finalised once ethical approval had been obtained in the UK. Pragmatic trial design, operative/ablative specifics were mainly at the discretion of the operating surgeon.
No trial specific monitoring was planned for the trial given the pragmatic nature of the trial however the sponsor reserved the right to conduct triggered site monitoring visits via the lead Dutch site should any concerns arise as a result of central monitoring processes.
Distribution of Trial Supplies
Participating sites had to have the ability to perform both trial interventions in order to be eligible to take part in the trial therefore no surgical equipment was provided. Electronic Investigator Site Files (ISF) were sent to international sites.
All sites sent completed Case Report Forms (CRF) directly to the Clinical Trials Research Unit at the University of Leeds. This data was then entered onto the trial database by dedicated data entry staff.
No samples were collected for central analysis in this trial.
Validated translations of patient completed quality of life questionnaires were used where available and combined into a booklet for each required time point, along with translated instructions for completion. The questionnaires used numerical scales and tick boxes (rather than free text fields) and the translated questionnaire booklets were laid out in an identical manner to the UK to facilitate data entry at the Clinical Trials Research Unit. The health economic analysis was planned to be performed from a UK NHS perspective, using only data collected from UK patients.
Data Ownership & Publication
All trial data was owned by the University of Leeds as host institution. Sites were not permitted to publish concerning their patients which was directly relevant to the questions posed in the trial until the first publication of the primary endpoint analysis. It was planned that all collaborators would be listed as contributors, with top recruiting investigators named as authors (subject to journal requirements).