PRED4 - rare adverse events studies

The UK IBD Genetics Consortium has started recruitment for the PRED4 study, which is now open in a number of sites. The team is currently busy opening the rest of the sites in the UK (similar to the 5-ASA-induced nephrotoxicity study). These studies are investigating drug-related rare adverse events and aim to identify clinically useful genetic markers that predict serious drug side effects, in particular:
• Thiopurine-induced pancreatitis
• Thiopurine-induced leucopaenia
• Anti-TNF-induced demyelination
• PPI-induced nephritis.

Further information can be found at UK IBD Genetics Consortium and in the attached file.

Two CCRN-supported hepatology trials

Primary Biliary Cirrhosis (PBC) Genetics and Primary Sclerosing Cholangitis Studies
Hepatology Specialty Group

The PBC Genetics Study is a national effort to establish a PBC DNA collection consisting of DNA samples from approximately 5000 patients with PBC. The study looks for variations in small fragments of DNA between 'healthy controls' and patients. The DNA collection will be used for a genome-wide association study (GWAS) of PBC and future genetic studies. Recruitment started in Cambridge, expanded to include East Anglia and transplant centres, and is now recruiting nationally. Getting the CCRN on board made an enormous difference to getting more participants into the study. We now have a co-ordinator in Cambridge who directs nurses around the country to identify patients and collect data, which he then collates. Recruitment in the fourth year of the study is now running at 60 - 100 patients a month with total recruitment at over 4,000 which (with about 12000 - 15000 patients recruited nationally) is staggering.

With CCRN resources and coordination by the Hepatology Specialty Group, we are taking a similar approach to a study on a similar disorder, Primary Sclerosing Cholangitis, and are successfully recruiting 50 patients per month. With 1500 patients already recruited, this study is on course to deliver on time and on target. If you have any queries on either of these studies then please contact This e-mail address is being protected from spambots. You need JavaScript enabled to view it , West Anglia Lead, Hepatology Specialty Group.

Clinical Trials Update #4 March 2011

Clinical trial recruitment to GI and hepatology trials across the UK has shown further promising increases. There has also been a significant increase in participating centres for multi-centre studies, and continuing progress in BRAG status (see bottom of article). Nationally the target of doubling recruitment to high quality trials has already been met, 18 months ahead of schedule. The only disappointments are the slow rate of expansion of the GI portfolio, and the relative paucity of commercial studies coming through.

Key Messages

The national GI and Hepatology Specialty Groups are keen that:

  • interested clinicians are encouraged to recruit patients and also have access to the NIHR CCRN infrastructural support.
  • any blocks to trial recruitment are highlighted: These can be fed to your local CLRN GI or Hepatology Specialty Group Lead(see link below) or to the Chairs of the Groups: Stuart Bloom (Gastroenterology) or Steve Ryder (Hepatology).

Anyone wishing to become involved in clinical trials will need to attend an on-line or in-person course on GCP (Good Clinical Practice). These are usually free from your local R&D Dept. Also see useful links below. Advice on trial set-up can be obtained from trial coordinators and local R&D teams. Most CLRNs have a lead for GI and Hepatology, and these individuals can advise on commercial studies and CLRN support funding. To find your Lead click here.

Recruiting to time and target - BRAG ratings

A national system of high level performance indicators has been developed to track which studies are broadly recruiting according to plan, and those which are falling behind with their recruitment and are at risk of not completing to time and target.

The UK has traditionally had a poor record of recruiting to time and target compared to other countries, leading to a loss of confidence of the pharmaceutical industry, with the potential that this could lead to a progressive reduction in commercial studies. Academically-led studies which fail to meet their targets often result in requests for further funding in order to complete, or may fail to achieve a statistically significant result.This is not cost-effective and participation of patients in a study which is under powered is unethical.

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