Title: What is the role of faecal calprotectin testing in primary care?
Funder: Department of Health and Social Care

Abstract: Background: Faecal calprotectin testing has been approved by the National Institute for Health and Care Excellence (NICE) for the differential diagnosis of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) in primary care in adult patients presenting with chronic unexplained diarrhoea. Faecal calprotectin is a marker for intestinal inflammation which can aid the selected referral of patients with a high probability of IBD into gastroenterological care while negative faecal calprotectin cases are managed as IBS patients in primary care. The approval was based on a positive cost-effectiveness assessment which was driven by a reduction in referrals and subsequent invasive colonoscopies compared to no testing. Due to limited available evidence from primary care studies the assessment assumed that the measures of test accuracy are transferrable from secondary care studies and that general practitioners (GPs) only refer test positive cases to secondary care. However, transferability of test accuracy estimates between settings cannot be assumed when patient populations differ between settings and emerging evidence suggests that assumptions of appropriateness of testing and referral in the assessment were overoptimistic. Aim: The aim of this proposed research is to re-assess the accuracy, use and cost-effectiveness of faecal calprotectin testing in primary care by addressing the uncertainties around test accuracy and patient management following testing and to understand GPs' views related to referral.Research questions: What is the referral rate of test positive / negative patients and what influences referral? What is the test accuracy of faecal calprotectin testing in primary care? What is the revised cost-effectiveness estimate of faecal calprotectin testing in primary care using outcomes from questions 1 and 2? Methods of investigation: Question 1 will be addressed by a GP database analysis of anonymised patient records of patients with at least one faecal calprotectin test recorded to investigate who GPs test, which patients GPs refer and what the patients' final diagnosis is. GPs' views and experiences related to referral will be investigated through semi-structured interviews with 20 GPs using the constructivist grounded theory methodology. Question 2 will use two approaches. The first will use a tailored meta-analysis of studies identified by an updated systematic review only including studies that are compatible with the test positive rate and prevalence found in primary care defined by information from the GP database. The second approach will explore the feasibility of using routinely collected data to derive test accuracy estimates. The study will use GP database records to explore test accuracy of faecal calprotectin testing in FC tested patients using colonoscopy, IBD specific medication and / or follow up to ascertain final IBD diagnosis. Positive predictive value, sensitivity and specificity will be estimated and a receiver operating characteristic curve will be developed to identify an optimal FC positivity threshold for primary care. Question 3 will bring together outcomes from questions 1 and 2 in a revised health economic model built for the assessment of faecal calprotectin testing in primary care. The patient perspective will be considered throughout the project by active involvement of a patient reference group in advisory meetings, in the formulation of questions for the semi-structured GP interviews and in the co-dissemination of research findings. Expected benefits to patients and the NHS: The revised cost-effectiveness model will provide improved knowledge on the cost-effectiveness of FC testing in primary care and on the appropriateness of testing by GPs. The NHS will benefit from this research through reduced referral rates by making available the research findings on test accuracy and test threshold to GPs increasing their knowledge and confidence in FC test use. This will optimise patient diagnosis and management with fewer inappropriate referrals to colonoscopy.

Lay abstract: Background General practitioners (GPs) can now use a new test in people with abdominal problems such as long term diarrhoea. It helps GPs to tell people apart who have one of two conditions: inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS). People with IBD have an inflamed bowel and need to see a specialist at hospital. People with IBS have no inflammation and can be looked after by their GP. This is why a correct diagnosis is important. The test is called the faecal calprotectin (FC) test. The FC test measures levels of a protein called faecal calprotectin in stool samples. Patients with an inflammation usually have high protein levels. GPs can use the test to identify these patients with an inflammation and send them to hospital for special tests and treatment. Patients with an irritable bowel generally have low faecal calprotectin levels. Because the test gives GPs this extra information, many patients with IBS do not have to be sent to hospital for their diagnosis. The test could help many IBS patients in getting a diagnosis and appropriate advice sooner without having to go to hospital for further tests. Why is this research important? The problem is that we only know how well the test works when it is used in hospitals because no study has tested how accurate the test is when GPs use it. It has been assumed that it works as reliably in GP practices but we do not know this for sure. It is possible that it does not perform as well because the many patients who see their GP are generally less ill than the few patients referred to a specialist at hospital. This is why I want to find out how accurate the test is when GPs use it in patients with abdominal problems and how GPs use the test result. Research plan I will look at evidence from a database that collects information from over 500 GP practices. This database includes details of millions of people from the UK who have agreed that their health information can be used in research. The data is anonymised so that researchers like me cannot tell who the data belongs to or which GP practice the patient attends. In the database I will identify all patients who have had an FC test. I will then investigate: what their symptoms were; what the result of their FC test was; whether they were sent to hospital; and whether patients were finally diagnosed with an irritable bowel or with inflammation of the bowel. I want to compare this diagnosis from the GP or hospital with the outcome of the FC test to judge how often the test was correct and how often it was incorrect in telling the GP to send the patient to hospital. This will tell me how accurate the test is. I also want to study whether GPs test patients that should not have had the test. For example patients who have problems that are so severe that they should have been sent to hospital without having to wait for a test result. And I want to find out how often GPs ignore the test result and send patients to hospital unnecessarily even though the test says that the patient has an irritable bowel. This means I do not just want to find out how good the test could be in the perfect world. I also want to find out how good it actually is in real life when GPs make the decision to use the test. To understand why and how GPs use the FC test I will interview 20 GPs.How accurate the test is and how GPs use the test information will affect the care of IBS and IBD patients. It might also have an impact on how much the NHS has to pay for this test. I will estimate this using the findings from my study. In order to ensure that my research is relevant and helpful to IBS and IBD patients I will ask patients to get involved throughout the research; in formulating the GP interview questions and in helping me interpret and present the findings. Study outcomes At the end of my study I want to be able to say: how well the test works for GPs; whether it was the right decision to make this test available to GPs; and what GPs need to know and change to get the most out of the test for their patients.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: ORAL AND GASTROINTESTINAL