Figure. Clinical trials for patients with stones.

The National Institute for Health and Care Research (NIHR) was formed in 2006 with the aim of delivering large research trials in the United Kingdom (UK). This has seen 3 large, randomized trials in stone disease funded in the last decade, 2 of which are published in high-impact journals and the other is eagerly awaited (see Figure). But that doesn’t tell the whole story of stone research in the UK, and in this article, I am also going to highlight the work of the British Association of Urological Researchers in Training (BURST) and The Urology Foundation (TUF) in driving forward clinical stone research in the UK, as well as discuss the 3 large NIHR studies. Of course, there are other trials taking place in individual units that cannot be mentioned in 1 short article, which is only focused on larger national studies.

The BURST Research Collaborative is an international group founded in 2015 comprised mostly of urological residents.¹ The aim is to produce high-impact multicenter audit and research which can improve patient care. This has been a huge success with several large studies demonstrating the power of this collaboration. Examples of early trials were IDENTIFY, a large multicenter study of 11,000 patients across 100 units in 26 countries to identify risk factors for cancer in patients presenting with hematuria.² This led to the publication of a risk calculator for use in patients with hematuria.³ In urolithiasis the MIMIC study analyzed 4,170 patients with acute presentation of stone disease in 71 centers across 4 countries, which showed no benefit to inflammatory markers C-reactive protein or white blood cell count in prediction of stone passage, nor was there a benefit to medical expulsive therapy.⁴ This also led to a risk calculator for stone passage in patients presenting with ureteric colic.⁵

TUF is a UK-based charity funding research, fellowships, and training in all areas of urology.⁶ In 2021 they set up the TUF Trials Unit with the aim of providing an infrastructure to take forward promising clinical research ideas from urology units across the UK. Following a competitive process involving The British Association of Urological Surgeons, TUF partnered with the Clinical Trials Unit in Aberdeen to act as their partner in taking forward these research proposals, and they currently have 15 projects that are being worked up in all areas of urology. One such project which has been proposed by BURST is to run a randomized trial in stent placement in uncomplicated ureteroscopy, a common clinical dilemma. However, at the time of writing, funding is still pending for this trial, and it is not clear if this will go ahead.

The Centre for Healthcare Randomized Trials is part of the Clinical Trials Unit in Aberdeen and was responsible for the 3 large NHIR-funded trials, with Professor Sam McClinton as the Chief Investigator for all 3 trials. The first was the SUSPEND trial, which was a multicenter trial of 1,167 patients in the UK randomized to tamsulosin, nifedipine, or placebo for patients with ureteric stones.⁷ This showed no benefit to medical expulsive therapy and was in keeping with other well-conducted large, randomized trials from Australia and the United States.

The second NIHR trial was the Therapeutic Interventions for Stones in the Ureter trial randomizing patients needing intervention for ureteric stones between shockwave lithotripsy (ESWL) and ureteroscopy.⁸ This trial, published in European Urology, showed noninferiority of up to 2 sessions of ESWL to ureteroscopy (with a noninferiority margin of 20%), although an absolute benefit to ureteroscopy of 11.7%. However, with overall success for ESWL of 77.9% in avoiding surgical intervention, this has shown the potential importance of ESWL in the acute stone pathway for these patients.

The third study is a clinical and cost-effectiveness trial for treatment of stones in the lower pole of the kidney—the PUrE study.⁹ This study, which has now closed and is awaiting publication, was comprised of 2 separate randomized trials. The first randomized stones less than 10 mm in the lower pole between ESWL and flexible ureteroscopy. The second, for stones between 10-25 mm, randomized patients between flexible ureteroscopy and percutaneous nephrolithotomy. Overall, 625 patients have been entered, and the results will surely advise clinicians and guidelines on how these stones should be treated.

In summary, the UK has produced 3 impactful high-quality randomized trials via NIHR funding over the last few years. But with the infrastructure in place to take forward clinical ideas and BURST showing the power of national and international collaboration, the future is bright for further important stone research from the UK.