Research Methodology

At the Centre for Evidence in Transplantation, we have an interest in the design and methodology used in transplant clinical trials, systematic reviews and clinical practice guidelines.

Some of our previous work has demonstrated that the quality of the design and reporting in transplant trials could be improved significantly. Many trials score poorly on methodological ratings scales, and even when the methodology is good, authors fail to report the results following the published CONSORT guidelines. Similar limitations can be found in many systematic reviews and clinical practice guidelines.

All of the randomised controlled trials, systematic reviews and clinical practice guidelines included in the Transplant Library are assessed by the CET team for quality. This information is made publicly available alongside the references in the library, to allow the reader to interpret the literature in light of it's methodological quality. It also allows us here at the CET to monitor trends in publciation quality over time.

Alongside this work with the Transplant Libray, the CET is also undertaking a number of projects that aim to assess and improve the quality of the evidence-base for solid organ transplantation. These are detailed below.

Kidney Transplant Priority Setting Partnership

One of the most important aspects of clinical research is to start with the correct questions, and to be trying to answer those questions that have the potential to have the biggest impact to patient care and outcomes. The Kidney Transplant Priority Setting Partnership (PSP) is a project that brought together healthcare professionals, patients and their carers to identify unanswered research questions and to prioritise these for future research. The PSP was funded by the Oxford Biomedical Research Centre, and followed the methodology outlined by the James Lind Alliance. It completed in February 2016.

A full list of the research priorities identified can be found here. A manuscript outlining the process has been accepted for publication in PLOS One, and the results of the process are already helping funders direct resources to areas identified of greatest priority.

Outcome Reporting in Transplant Clinical Trials

Interpretation, comparison and combination of results of clinical trials is reliant on accurate and complete reporting of outcomes. There is a great deal of variability in the consistency and completeness of outcome reporting in clinical trials, a problem that has extended to transplantation. Incomplete outcome reporting is a problem, as it prevents the inclusion of studies in meta-analysis and can open the possibility of outcome reporting bias.

Funded by a grant from the Alison-Hansen foundation, the CET undertook an analysis of outcome reporting in renal transplant clinical trials over a 5-year period between 2010 and 2014. Of the 4760 outcomes analysed, around 10% had missing data. Many outcomes were poorly defined, and over 30% manuscripts did not report a primary endpoint. In particular, safety and patient reported outcomes were very poorly reported, with only 5 of 182 studies reporting quality of life on a validated scale.

In an attempt to address this problem, the concept of "core outcome measures" has been developed. Core Outcomes are those that are deemed important enough to be included in all clinical trials in a particular clinical area, agreed by consensus between professionals and patients. The Standardised Outcomes in Nephrology (SONG) initiative aims to develop a Core Outcome Set for trials in renal transpantation (SONG-TX). The Centre for Evidence in Transplantation is collaborating in this important project.

Quality of Clinical Practice Guidelines in Transplantation

It is well recognised that Clinical Practice Guidelines in many areas of medicine vary greatly in their scope and quality. In particular, the evidence-base upon which guidelines are created is often questionable, with expert opinion often preferred over robust published evidence from RCTs and systematic reviews.

Transplantation is an area where guidelines are very important, and there are a large number published by a number of national and international organisations. The CET has embarked on a project to appraise the quality of transplant guidelines, using the AGREE II tool, in order to inform the transplant community and guideline developers where improvements are needed. The quality assessments will also be published alongside the guidelines in the Transplant Library, so that those using the guidelines for clinical practice can see the methodological rigour of the guideline development process when making clinical decisions.