Novel recruitment method helps to identify participants for Crohn's and Colitis research
Currently one in 250 people in the UK are living with a bowel and intestine condition. Many different treatments aim to ease the symptoms, but not all treatments prescribed are without a risk of side effects. We took a look at a study that could lead to a test that predicts if a patient is likely to encounter a side effect or reaction to a prescribed drug. It could also provide a new and innovative recruitment model for future research.
Crohn’s disease and Ulcerative Colitis are the two main forms of Inflammatory Bowel Disease (IBD) and are chronic inflammatory conditions of the gastrointestinal tract. Crohn’s is a debilitating disease that causes inflammation of the digestive system or gut. Many clinical research studies have resulted in the development of safe and effective drugs for thousands of patients living with Crohn’s and Colitis over the years, but with no breakthrough cure for the condition. Often patients are taking medication to reduce pain and inflammation for the rest of their lives with some suffering side effects as a result.
So, imagine if as a patient with Crohn’s or Colitis, you could be offered a simple test before being prescribed any medication, and the test result would identify if you are likely to experience any side effects? A NIHR Clinical Research Network (NIHR CRN) supported study set out to do just that.
"I had never felt so low since being diagnosed with Crohn’s. Predictive genetic testing could have made things far less painful and had less of an impact on my life. It would bring so many benefits, in particular being able to determine the best course of treatment.”
Dr Tariq Ahmad is a Consultant Gastroenterologist at the Royal Devon and Exeter NHS Foundation Trust, and is the Chief Investigator for the PRED4 study (Predicting serious drug side effects in the treatment of ulcerative colitis and Crohn’s disease) which opened in March 2012. Dr Ahmad, who is also a NIHR CRN National Specialty Lead for gastroenterology, explains more about the background to the study:
“For the majority of patients, side effects are mild and self-limiting, however a small minority of people experience more serious side effects requiring hospitalization and drug withdrawal. At present we do not fully understand why some patients experience serious side effects whilst the majority of patients tolerate the drug without problems.
“The PRED4 study set out to investigate whether there is a genetic basis for these side effects and ultimately might lead to a test to predict patients at risk of developing side effects. At risk patients might then be offered alternative safer treatments, or monitoring might be intensified.”
Each participant on the study was asked to complete a short questionnaire, donate a blood sample for DNA analyses at their local hospital and give permission to allow review of their medical notes as part of the study.
Lisa is a patient at the Royal Devon and Exeter NHS Foundation Trust who took part in the PRED4 study. She was diagnosed with Crohn’s disease in 2008 and has taken six different types of medication to help manage her condition. Lisa has unfortunately suffered many side effects and talks to us about her involvement in the PRED4 study and what the outcome could mean for her:
“Since diagnosis in 2008 I have struggled to find a treatment that has not given me considerable side effects and impacted on my life in some way. Over the years I have experienced flu like symptoms and excruciating abdominal pain which resulted in me attending A&E for emergency treatment due to suspected pancreatitis, which took several weeks of recovery.
“Since then I have tried other drugs and have suffered with terrible side effects, including a drug induced liver injury revealed by tests. After starting on anti-TNF treatment (a class of drugs used to treat inflammatory conditions) I felt well for a few years and was able to build up antibodies, however, during this time I developed recurrent ear and respiratory infections and swelling.
“Due to taking Infliximab in the last 18 months I have developed psoriasis, which has had a profound effect on my life, and I started losing my hair, and had to stop exercising which I loved. Suffering from this brought me to my lowest point. I had never felt so low since being diagnosed with Crohn’s. Predictive genetic testing could have made things far less painful and had less of an impact on my life. It would bring so many benefits, in particular being able to determine the best course of treatment.”
Identifying patients with Crohn’s or Colitis was a necessary step for recruiting participants to this study, Dr Ahmad and his team needed to study a large number of patients with Crohn’s or Colitis who had suffered a range of rare drug side effects.
More than 1,700 participants have taken part in the study, which was more than planned.
So how was the study team so successful in reaching this specific patient population? Dr Ahmad explains the impact of NIHR infrastructure:
“The first method of recruitment was by using the help and support of healthcare professionals in local hospitals, using searches of pathology systems and (electronic) patient records. Although this approach is often described as the ‘normal’ route to identify study participants, without the support of the NIHR CRN, we would not have got so many of the trusts on board so quickly. However, we knew we needed to develop other avenues in order to identify patients.”
The NIHR CRN has developed close relationships with many charities and societies through collaboration and partnerships in research, which helped Dr Ahmad and his team work more closely with the Crohn’s and Colitis UK (CCUK) charity. Dr Ahmad adds:
“This was an integral part of the recruitment success for the PRED4 study, which in turn enabled us to engage with over 40,000 members through newsletters and social media. We also worked with the UK Kidney Association patient group and advertised directly to patients via the research group’s own website which generated patient led recruitment particularly through social media.”
Looking to more innovative methods of recruitment for the study, the study team also took on a novel approach to recruitment using the Yellow Card reporting system, which enables users of prescribed medicines and treatments to log any side effects they may have experienced as a result of taking the drug. The yellow card reporting system is an online service, making it accessible to patients and the public 24/7, and is vital in helping the Medicines & Healthcare products Regulatory Agency (MHRA) monitor the safety of all healthcare products in the UK.
June Raine is Director of Vigilance and Risk Management of Medicines at the MHRA. June explains the process of using the yellow card reporting system for the PRED4 study:
“For this particular study the PRED4 team requested Yellow Card data in order to try to identify specific genes which cause Adverse Drug Reactions (ADRs). We’re really encouraged that this process has been positively received by the PRED4 team and would be pleased to contribute to other studies in which Yellow Card data can be used to aid clinical research and improve patient safety in the UK.”
While using yellow card data has proved beneficial for the PRED4 study, it may also be something that other researchers want to consider for identifying potential participants for future studies. Dr Ahmad concludes:
“The Yellow Card Reporting System was an absolutely necessary route in to access the patients we needed to identify for the study. Following approval of using this method of recruitment by the MHRA, we were able to use the Yellow Card database to identify potential patients.”
PRED4 has already reported results for its study of thiopurine induced pancreatitis and 5ASA induced kidney injury. Further data reporting the genetic basis of thiopurine bone marrow suppression and liver injury will be published in 2017 promising safer cost-effective use of azathioprine and mercaptopurine drugs. The study will remain open until 2018
The Yellow Card reporting system can be found at: https://yellowcard.mhra.gov.uk/idap.