Perspective 2019

IN THIS ISSUE ...Case Studies, Reports, Clinical Updates, Expert Opinion A New Pathway for Faecal Calprotectin Testing in Primary Care - Academic Health Science Network 2-3 Are You Fed-up Waiting for Results? Get Answers Faster with Point-of-Care Testing 10-11 Introducing Patient Home Tests for Calprotectin in a Routine District General Hospital 4-5 The FIT Revolution - Coming to Your Practice Soon Update on the NICE FIT Study 12-13 Calprotectin Self-Testing Four Years On Benefits for Patients and Healthcare Staff 6-7 How Low Can FIT Go? The Clinical Value of Low Level f-Hb Reporting 14-15 My Year with IBDoc® A Patient’s Perspective on Calprotectin Self-Testing 8-9 Resources 16 GASTROENTEROLOGY CLINICAL SUPPLEMENT 2019 Alpha Laboratories Ltd Patient Centric Diagnostics to Support Clinical Decision Making

PERSPECTIVE 2019 2 “The development of this algorithm offers significant benefits to the patient’s experience along with savings across the health economy. Its adoption by clinical colleagues is welcomed.“ 2 A recent publication from BIVDA and Innovate UK1 identifies three simple tests that could save the NHS £6.9 Billion over a 5 year period if implemented more widely. Faecal calprotectin is one of the tests heralded and it alone is estimated to offer savings of £65 million to the NHS. This could be achieved if calprotectin testing was more widely available to assist in the diagnosis of Inflammatory Bowel Disease (IBD). Although calprotectin is now well established and routinely in use in many hospitals, it is often restricted as a secondary care test. However, if calprotectin was made available more extensively as a primary care test then significant savings could be achieved in outpatient and colonoscopy resource. The challenge is that uncontrolled access to faecal calprotectin testing could result in an increase in cost and greater demands on limited resources (<50µg/g is widely accepted as a negative result, but this doesn’t mean that >50µg/g is positive). In order to address these issues a new pathway for the use of faecal calprotectin testing in primary care is being rolled out across England through the national Academic Health Science Network (AHSN). See Figure 1. The pathway is designed to provide GPs with a risk assessment of a patient’s likely condition based on the results of the faecal calprotectin test. This helps to provide greater confidence in decisions to refer patients to secondary care. The new pathway will help assist in cases where there is uncertainty between the diagnosis of Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD). An NHS England Task and Finish group has been formed to create a consensus report on optimising faecal calprotectin testing using this new pathway. The paper is available through the primary care commissioning website2. It has been endorsed by NICE, Crohn’s and Colitis UK and the British Society of Gastroenterologists. Health Economic studies demonstrate considerable financial benefits for primary care, capacity benefits for secondary care and most importantly, better patient experience, through faster diagnosis. Highly significant is the reduction in the number of patients who need to undergo risky , uncomfortable and costly colonoscopies. In the roll-out of the York Faecal Calprotectin Care Pathway (on which the above algorithm is based), compliance was 85% and so the actual (rather than optimal) saving amounted to between £60,000 and nearly £100,000 per 1000 patients. These savings were achieved by correctly supporting the diagnosis of IBS within primary care, avoiding 100–150 colonoscopies and 140–190 gastroenterology outpatient appointments. The AHSN Network is actively engaged in supporting the roll out of this improved pathway across the country after work in Yorkshire and Humber demonstrated significant benefits to the health economy in the region. If you would like to get involved in delivery of the pathway across your area, or want any further information please contact your local AHSN or email Victoria Hilton at A New Pathway for Faecal Calprotectin Testing in Primary Care Improving Patient Care and Access, Saving the NHS £65M References 1. BIVDA and Innovate UK: Three simple tests could save the NHS at least £6.9 billion. 2018 2. This issue of Perspective brings together real life case studies from nurses, clinicians and a patient, who discuss developments and changing opinions in diagnostics for digestive diseases. From improved patient well being, efficiences in clinics and potential savings in money and resources from the reduction in colonoscopy requirements, advancing technologies in calprotectin and faecal occult blood testing have a lot to offer. Alpha Laboratories has worked in partnership with clinics and laboratories over many years to champion calprotectin testing for differentiation between IBS and IBD. Our extensive range of standardised assays from BÜHLMANN provides solutions for improved patient care and management in both screening and monitoring applications. At the forefront of faecal testing, we have been involved with the National Bowel Screening Programmes since 1998; originally supplying the guaiac-based test and now the quantitative faecal immunochemical test (FIT) in Scotland and Wales. Close relationships with key opinion leaders and external quality assurance schemes ensure the company is always at the leading edge of diagnostics, and continues to be subject matter experts in the implementation of FIT for symptomatic and screening programmes. for reducing colonoscopy referrals. 3 BÜHLMANN calprotectin assays are standardised between formats, so from point of care to high throughput laboratory testing, results are consistent. Find out more about the full range of calprotectin assays and read user case studies at Figure 1. Faecal Calprotectin Algorithm Red Flag Indicators ï Unintentional weight loss ï Rectal bleeding ï Family history of bowel/ovarian cancer ï Anaemia ï Abdominal/rectal mass ï Nocturnal symptoms ï Raised inflammatory markers ï Bloody diarrhoea ï Systemically unwell Symptoms of IBD or IBS Age 18 - 60 with diagnostic uncertainty ï If cancer suspected: 2 week cancer referral ï If acute severe IBD suspected then urgent IBD referral Yes No Primary diagnostic: FBC, CRP coeliac screen, stool MCS, U&E, Bone profile, TFT Negative Positive Treat as appropriate Faecal calprotectin (FC) FC<100 FC 100-250 FC>250 Clinical Review Repeat within 2 weeks IBD unlikely FC<100 FC 100-250 FC>250 Manage symptoms locally Symptoms persist FC <50 AND age <50 consider second line therapy for IBS before referral FC >50 or age >50 Routine referral to gastroenterology Urgent referral to gastroenterology

4 PERSPECTIVE 2019  4-6 Weeks Wait for a Send Away Result Introducing Patient Home Tests for Calprotectin in a Routine District General Hospital Pearl Avery, Lead Inflammatory Bowel Disease Nurse, Dorset County Hospital and Gastrointestinal/IBD Nurse of the Year 2018 Pearl Avery is based at Dorset County Hospital in Dorchester. In 2018 she received the Gastrointestinal/IBD Nurse of the Year award from the British Journal of Nursing. Pearl’s nomination resulted from her strive to provide the best care possible for patients in her local service. This included her pioneering work to introduce a new IBD patient management system which has earned national recognition1. It incorporates the IBD registry and the BÜHLMANN IBDoc calprotectin home test. Pearl tells us about the impact that the introduction of IBDoc has had for both patients and staff. “Prior to the introduction of the IBDoc home test, all our calprotectin tests were sent to an external provider. So the stool samples were collected by the patient and then dropped off at the GP, who would send them to Dorchester Hospital on the transport run. The lab would then batch the samples and send them to the external provider for analysis. Due to this process it would take anything between 4 to 6 weeks before we received a result! Having the calprotectin result was good, but it was historic, relating to the clinical situation 6 weeks previously rather than currently. So the patient’s condition may have improved or got worse in the interim. Some patients can have high calprotectin levels whilst exhibiting few symptoms, but in our experience it is still a good indicator that they will relapse in the near future. These cases are a real worry as the patients that feel well but have a high calprotectin level can end up having a bowel perforation. If there is a delay between the rise of the calprotectin levels and the onset of symptoms, having test results available much sooner would give us the opportunity to take action. Without a Calprotectin Result Treatment Decisions are Difficult We have been introducing the IBDoc system slowly for the last six months and uptake has been really good. Originally we had planned to get patients to bring in a sample and we would do the tests in clinic. However, 95% of patients enrolled so far are doing the test themselves at home. The procedure is quite simplistic – I train the patients using the basic pictorial guide that is in the kit which roughly takes 10 to15 minutes. It really makes it very simple. If I have any advice for other IBD nurses it is to do this early on in the consultation so that you have time to complete it and you can manage your time more effectively. We currently have around 1300 patients who attend the clinic and in the 6 months we have been using the IBDoc we have rolled it out to 97, so it will probably take a couple of years to switch things over completely. The focus so far has been with the patients who are taking biologics and my next goal is those who are on azothiaprine as they also need close monitoring. The main group of patients on the biologics tend to be slightly younger and so you might expect this demographic to respond better to App technology. However, we do have some older patients who are quite techno-savvy and have smartphones. Obviously it won’t be for all, but it has surprised us how well some of the older patients have responded. There will be those who won’t want to do it as we expand the test out, but at the moment we are probably enrolling those who are more likely to want to be involved. Patient Self-Management Obviously a big reason for us to switch testing methods was the time frame for the availability of results, but there is also a growing patient voice that wants to be self-managed, less reliant on health care professionals and waiting for results. Being in control and getting immediate results reduces anxiety for them ■ We do have one patient who studies away and he has taken a few tests with him. One test has already been done because he didn’t feel well and it gave a positive result, although it was less positive than the previous result. This then allowed us to reassure him that the treatment plan was working and to persevere because he can see the progression in a tangible fashion. ■ One of the doctors wanted to stop the azothiaprine on a patient who had been on the drug for several years. The send away calprotectin had been normal and the colonoscopy was normal, but the patient was really nervous. We managed to persuade the patient that she can have an immediate test if she feels unwell, so it has been agreed she will stop the drug and do an IBDoc test in 7 weeks and see me a few weeks after that. She can take the test at home so that if she feels unwell then she can check her calprotectin level at any time. She went away much more reassured. Simple step by step pictorial guide instructs patients how to use the IBDoc calprotectin test Pearl Avery with her IBD Nurse of the Year 2018 Award

Find out more at 5  One patient who phoned our helpline, because she was quite anxious and unwell, did a sample and brought it into clinic for testing. The result was actually negative so we were able to provide immediate reassurance that her symptoms were not due to the IBD and advise her on her other health issues. Previously we would have expected to receive at least one call a week until the results were back. In this respect I would say that IBDoc has definitely affected how we are working. This is something that we can monitor, capturing both the helpline and email enquiries. Now I have 97 patient emails and I send a message to say I have noted your result etc. and they will respond by email. So we are changing the traditional communication method. Previously people would be calling – this isn’t something we had anticipated. It is going to be hard to quantify but I will say it has definitely had an impact. Visibility of Results In the beginning we didn’t allow patients to see their results but now we are allowing patients to view the actual results and they seem to like that. For me the traffic light system is really useful to inform both the patient and the clinical team what to do: ■ Red - we know we have to act immediately ■ Amber - we send an email to say the calprotectin level is a little high but we aren’t worried. We can retest in a month and if it is still high then we can consider what to do ■ Green - that is great because the patient is reassured that their calprotectin is below the cut off value. The traffic light system gives us a clear signal and we normally have so much data to manage that infographics are becoming an increasingly important way to help us to manage things. Cut-Off Values Currently the cut-off is set at 100 and 300µg/g which is the default setting. However, nearly every patient who has had their treatment escalated to biologics or immunomodulators, had calprotectin levels above 400µg/g. So we may review the cut-off moving forward, especially as recent publications on treat to target strategies have used a cut off of 250µg/g to indicate remission. The IBDoc won’t change how we manage patients presenting with acute symptoms. They will still have a flexible sigmoidoscopy within 3 days even if a calprotectin result is available, because we really need to understand what is happening with these patients. What it might enable in the acute A&E setting is to prevent patients going down the surgical route. Because we can act quickly on the calprotectin result IBDoc gives us the ability to Treat to Target – we had a least one patient like this in the original pilot study. Compliance with testing can be a significant issue. For example in a clinic of 10 patients; 2 of them who were asked to do calprotectin didn’t, although this isn’t necessarily related to the method of testing. We may want a baseline test for patients that are well, but since they are not feeling ill they don’t want the trappings of disease. They want to forget that they have IBD so even with the IBDoc they may still not complete the test. There are also some patients who will never do these tests because they don’t want to know the result even if they are well. One of the messages we as nurses need to get across is that even if the test comes back negative we will never ignore patient’s symptoms. Sometimes the patients don’t understand what the calprotectin result is telling them i.e. that the symptoms are not caused by inflammation but some other gastric disturbance that needs managing differently. There will always be patients who don’t comply and maybe we should be targeting these people because if they take control then hopefully they will be more compliant in the future - but that is an ideal world. Treat to Target In the six months that we have been working with the IBDoc, one patient was saved from hospital admission. It looked like they were having an IBD flare but the symptoms were actually being driven by something else. With another patient whose calprotectin results were >1000µg/g we were able to put them on the right treatment (steroids) quickly enough to stop the progress of the disease. The patients who have seen the most benefit from the introduction of the IBDoc are obviously those on biologics because it enables us to monitor them more easily. There are also the patients who we are trying to help understand that their symptoms can be functional and that we will manage them in another way. The advice I would give to other clinics who are considering introducing the IBDoc is: ■ Ask the point of care manager to negotiate with the laboratory on your behalf ■ Build your case around patient care and improving outcomes ■ Demonstrate how it can potentially impact the hospital finances – it only takes one hospital admission to be prevented or one patient where you can de-escalate treatment and significant savings can be made. If we can get 50% of the patients on board I will see it as a success. If we can get our IT in place then it will really improve the benefit of the self-monitoring. I don’t see that we have any choice but to make these changes to ensure a sustainable NHS, because the number of IBD patients is only increasing. Until we find a cure for IBD we have to find better ways to manage the chronically ill that are well and keep them out of hospital, so that we can focus our resources on the chronically ill that aren’t well. Reference 1. Dorset Echo 23rd March 2018 Clinicians can control how the patient sees their result: Test Completed, Traffic Light or Quantitative µg/g Result

6 PERSPECTIVE 2019  Calprotectin Self-Testing Four Years On The Benefits for Patients and Healthcare Staff of Routine IBDoc Use Kathleen Sugrue, Advanced Nurse Practitioner at Mercy University Hospital, Cork The Mercy University Hospital in Cork is a designated Gastroenterology Centre of Excellence and has one of the largest cohorts of IBD patients in Ireland. It was the first hospital to introduce the BÜHLMANN IBDoc® calprotectin patient self-testing into routine practice. This was back in the summer of 2015 and after 4 years the team there has gained a wealth of experience in the value of this test for monitoring their IBD patients. Kathleen Sugrue, the advanced nurse practitioner in IBD at the Mercy talks to us about how implementing IBDoc testing has positively impacted the patients and the clinic. Historically we used an external laboratory for calprotectin testing (Biomnis). However, this was extremely expensive and we were waiting 6-8 weeks for the results. This is too long to wait for clinical decision making. We first introduced use of the IBDoc test in the summer of 2015. After an initial trial period it was rolled out to all IBD patients that have compatible phones for reading the results. There are now over 50 devices that support the CalApp® and so we now have over 650 patients that are regularly using the system. All initial patient screening tests are now performed in our own laboratory, since calprotectin has been introduced in-house. This is using the BÜHLMANN fCAL turbo assay which has the advantage of being standardised with IBDoc. Once a patient has been diagnosed we would hope to get them onto the IBDoc system for monitoring. However, we don’t have funding for all patients and there are some that don’t have compatible phones, so we still use the lab as a fall back for these patients. Costs are similar for the two test formats but we do prefer to have patients on IBDoc, in terms of ease of testing and speed of the result. Thus we always try to use IBDoc as a priority wherever possible. Initially patients can be a little taken aback when they realise that they will do the test themselves but you explain that it isn’t much different from them taking their sample for the lab test. Most of them are familiar with having to provide the samples anyway so it is okay. The only extra bit they have to do is reading the result with the phone and actually they embrace it. For patients that are well, we use IBDoc to monitor their disease and we explain that without it they will require a colonoscopy; the vast majority are happy to do the test – the chance of avoiding a colonoscopy is a good motivator. Display of Results In the beginning we started with the traffic light system of results, but we found it somewhat restrictive. For example a patient could have a red result and a few weeks later test again and still get a red reading. What they didn’t see was that their actual calprotectin level had reduced from >3000µg/g down to 700µg/g, so it was in fact trending in the right direction. In the interests of transparency, selfmanagement and having a better understanding of their disease, patients are now able to see the numerical result which is very important for reassurance. Patients who are using IBDoc generally test a base line level on initiating their treatment with biologics and then re-test every four months. As a general rule we use four tests per patient, per year. The 4th test they keep at home to use if they having symptoms. Thus, if they aren’t sure if they are flaring or not they can use the test for reassurance. Funding The biggest issue we have at the moment is funding, despite the fact that IBDoc is cheaper than the previous method of testing and we are making significant savings on the use of biologics. We still don’t have a direct source of funding for the test (although we have had agreed an additional member of staff which will help significantly). Some of the pharma companies will fund patients on their drugs, and I am in discussion with some others so that all the biologics patients have access. However I would like the IBDoc for all IBD patients as it isn’t fair to have the test available for one cohort of patients and not another. I am hoping that it will become part of the care programme for all patients, but there is currently no funding for this. Patients love the IBDoc and have become reliant on it for selfmanaging their disease. Once they get started on it they don’t want to stop using it. I have even had patients enquiring about selffunding the tests because the cost isn’t huge for 3 – 4 tests a year. Unfortunately we currently don’t have the ability to bill patients for it so this isn’t happening here. The feedback from the Gastro team and other IBD nurses is also extremely positive: ■ Patients are more confident at self- managing ■ We aren’t having to chase results ■ Patients email if they get results they are concerned about, so it is a very safe system Sometimes you are investing a little bit more to make sure the longer term outcome is better. We do have a conversation with them about the testing and this takes a bit of time, but it is worth it in the long run as patients are with us for life. It saves us time going forward as we are not chasing results from the lab all the time. Patients love the IBDoc and have become reliant on it for self-managing their disease. Kathleen Sugrue (3rd from the left) and the IBD team at Mercy Hospital

Find out more at 7  Initially we went through the formal training, but now we give the patients the kit and say watch the video and 9 out of 10 don’t have any issues with these instructions. Reduced Helpline Calls Since introducing IBDoc we get less calls on the helpline because patients can check themselves if they are concerned they are flaring. More than fifty percent of the time they do not have active disease – perhaps it is something they have eaten or they have a bug. Once they know it isn’t their disease then they don’t contact us. The other really big positive for us is the fast track clinic. We ask patients to do the IBDoc test before they come to clinic. When we have the calprotectin result readily available to make clinical decisions we can make a definite plan immediately. Previously they would have come to clinic and we would have been waiting 6-8 weeks for a result, so it is much more efficient for them to come in with their own result. During the two month period from February to March 2019, 27 patients who experienced symptoms of a flare-up did the IBDoc test and had normal results. Therefore they did not need to come to clinic. This is an example of considerable saving in terms of both financial cost to the hospital and also Gastroenterologist and IBD nurse time. Dr Elsafi from the Mercy conducted a study using IBDoc to indicate mucosal healing in IBD patients starting biologics1. Traditionally patients starting biologics have follow-up clinic appointments at 3 months and a colonoscopy at 6 months to assess mucosal healing. During the study 131 patients were provided with IBDoc kits, enabling them to test their own calprotectin levels at home at the 3 and 6 months post induction of biological agents. This avoided the need to attend hospital appointments to obtain a calprotectin result. Results from the IBDoc tests were transferred to the gastroenterology team’s database. At the 3 month assessments the IBDoc results showed that 40% of the patients had normal calprotectin levels. After 6 months 75% of the patients showed normal calprotectin levels [Figure 1]. Of the 78 patients that had a raised IBDoc calprotectin at 3 months, 28% of these had a normal reading after 6 months. Overall, using the IBDoc calprotectin results as indicators of mucosal healing, a total of 53 clinic visits and 62 colonoscopies were not required because the calprotectin results were within normal limits [Figure 2]. This represents a significant cost saving plus the benefits of better managed healthcare resources, reducing demand and therefore the waiting times for both clinic visits and colonoscopies, plus an improved patient experience. Guidance on Treatment Plans We also use IBDoc to guide decision making on switching treatments if a patient is on a biologic and isn’t doing so well from a symptom point of view. If the IBDoc result shows the calprotectin is high or continues to stay high then we would use this as justification to switch to another medication or for treatment escalation. Virtual Clinics At the Mercy we hold virtual clinics for patients who are in remission for at least six months and IBDoc is an essential component of being able to do this. The patients are sent an IBDoc kit in the post and an IBD questionnaire; they also get bloods done by their GP. A date is arranged for a call and we go through the results, ensure they are doing well and that no changes are required to the medication. After the call I dictate a letter to the GP to say they have been reviewed at a virtual clinic and outline what the outcomes are. Cost Savings We currently have more than 100 patients who are assessed on a virtual clinic basis. This is expected to increase as there are significant resource and cost savings using this approach. The cost of an outpatient clinic appointment in Ireland is €129.50 and that is without lab work or anything; with this level of saving it is definitely the way forward and the ability for remote testing is a key element of this. If clinics are considering implementing patient self-testing, my advice is - just do it. Talk to other clinics who have been using it and you will see very quickly how easy it is. The buy in from patients is very positive and overall it makes things easier from a healthcare point of view. Reference 1. G Elsafi. UEGW 2017. Cost effectiveness of IBDoc as a surrogate marker of mucosal healing in IBD patients post induction of biological agents. % of Patients with Normal IBDoc Calprotectin Levels Figure 1. Normal IBDoc results in IBD patients 3 and 6 months following initiation of anti-TNFα therapy. No. of Appointments Not Needed Figure 2. Clinics and colonoscopies saved through patients using IBDoc calprotectin home tests. If clinics are considering implementing patient selftesting, my advice is - just do it.

8 PERSPECTIVE 2019 I am a 48 year old male living in the Manchester metropolis. I have two beautiful children, an incredible wife and a loving, close family. I have had the misfortune of having Crohn’s disease for the last 27 years; I have had two resections, the first resection in 1992, and the second in 2001. I was in remission for 9 years until a severe flare in September 2010. Since then I have been battling this disease, physically, mentally and emotionally. I have tried steroids, helminths, azathioprine, 6mp, biologicals, anti-map, LDN … you name it …but the side effects have most often outweighed the results. The most successful tool which I keep returning to is control by diet, this takes incredible will power to stick to and monitor. Calprotectin Monitoring On the quest to control my Crohn’s disease through diet, I have used calprotectin tests to effectively monitor my Crohn’s symptoms over the years. I was fortunate to work with Professor Hunter for three years who first introduced me to the calprotectin test via a clinic in London. I learnt some fundamental pointers about my disease activity: ■ I was well (ish) if I could keep my calprotectin to 50µg/g – 250 µg/g ■ If I introduced a food over a week that created inflammation in my gut the calprotectin result would shoot up to over 1000 µg/g ■ If I stuck to my diet rigidly it would drop back down to 70 µg/g and If I kept ‘cheating’ here and there I would receive results around 800 µg/g For me this kind of data is invaluable and reduces the anxiety of not knowing if you are making your condition worse, which can be a significant part of having IBD. Every month or so I would send a sample to the labs and a week later I would have a result that I could act on. The actual clinic could turn the results around in forty-eight hours but posting it to London added an extra day. The real time delay of process though, was the administration; the results going to the professor, then to my GP, and eventually to me. Now, when I do a calprotectin test (currently managing via diet and vedolizumab), assuming I can get the Calprotectin to as low as 50 µg/g I know I am not increasing the length of inflammation in the bowel. It is through this deep understanding of my individual Calprotectin results I am confident that the Crohn’s remains contained to a specific length of bowel and hasn’t increased now for over five years. So I need to stick with the diet but I do need to introduce more foods. I have been on a very basic LOFFLEX diet of rice, chicken and carrots; every time I introduced a food I would have to report back to the dietician every six weeks but it was just too long to achieve sensible conclusions. IBDoc® Calprotectin Home Testing So a while back I wrote an impassioned article for Alpha Laboratories, publication ‘Perspective’, with the headline ‘IBDoc® will change people’s lives but only, if patients can monitor instant results’. I had been prompted to write the article on hearing about IBDoc, the inflammatory detection system using calprotectin, developed as a home testing kit. Unfortunately I was instantly disillusioned on hearing that my clinic could not give me access to it. However, I’m sure you’ve heard the old adage, “you create your own luck”. As with many fellow IBD sufferers I have a determination and resolve to break through the admin barriers to get results and that article led to the amazing opportunity for me to test IBDoc as a Crohn’s sufferer. I am delighted to report I have been using IBDoc roughly once a month for over a year and it’s now time to share my findings. I have been eating rice, chicken and carrots for so long my body seems to react to anything new I put in it. The obvious route now is a full re-introduction of food groups back into my diet. But are they causing inflammation or have I developed intolerances? It’s the great unknown but with IBDoc at least I can understand what’s going on. Peace of Mind The number one thing for me since beginning the IBDoc trial is that I have found that my anxiety levels have dramatically decreased. I haven’t felt the need to call the IBD helpline or prompt my GI secretary to try to move my next appointment up. Of course the reason being in no small part due to the IBDoc. It has reduced the “waiting time” for results down to hours instead of days or weeks. This means I’m not constantly second guessing or monitoring how I feel, which I find mentally exhausting. My Year with IBDoc® Lee Stanley, long term Crohn’s sufferer shares his experience of managing his disease with the help of calprotectin self-testing.   The reassurances the [calprotectin] result provides for me is priceless. For the first time I can actually have a small understanding and control of what’s going on in my bowel without visits to the MRI scanner or the dreaded colonoscopy.

Find out more at 9 I’m also very mindful that my fantastic GI team don’t have the resources to be on hand 24/7. So that pain I had felt last night or that extra trip to the loo now doesn’t result in me calling my IBD nurse for reassurances she can’t give me. On reflection I haven’t called my IBD nurse once since I began the IBDoc trial. I believe what IBDoc has allowed me to do over the course of the last year is fundamentally educate myself in understanding my disease state. I now have just over a years worth of hard data to discuss with my GI. [Figure1] Looking at my data for the year, we can clearly see that I’ve managed, with medication and diet to remain roughly between “Normal” and “moderate”. The average result over the course of the year was, 138µg/g; I consider this to be satisfactory (apart from the huge spike which was due to an Easter meal), as my GI is comfortable with results below 200µg/g. Crohn’s disease is a physical condition, we know that of course, however one cannot underestimate the mental pressures this disease presents. So I may have an upset stomach or my bowel movements may have increased or I may feel nauseous, but I know after a year of using IBDoc I’m not going to end up in A&E with a stricture or spend weeks on a ward waiting for invasive procedures to tell me I have little or no inflammation. The symptoms are caused by things other than the Crohn’s, so there is no need to panic that things are moving out of control. Figure 1 Monitoring calprotectin levels over a year using home testing. Screen shot from the IBDoc App A Powerful Tool Having Crohn’s disease for twenty-seven years has taught me many things; fundamentally that patients need to self manage and IBDoc is one powerful tool in my self-managing tool kit. I wasn’t expecting IBDoc to provide me with the answers to everything; using IBDoc I haven’t suddenly found a miraculous cure, I’m still searching for the “perfect” diet and optimised plan. However, I believe IBDoc has contributed significantly to both the physical and mental aspects for the management of my disease. Follow my continuing journey, on my blog: Chrohn’s-disease-me-and-ibdoc.html IBDoc® Patient Self Tests: ■Quantitative rapid test ■Excellent correlation with laboratory based tests ■All components contained within each kit ■CE marked See what IBDoc can do for your patients To find out more please visit If you are interested in evaluation of IBDoc in your clinic please email Stay Ahead of the Game with IBDoc® Remote Management for IBD Patients Improve Monitoring ■ Monitor mucosal health ■ Predict flares ■ Optimise treatment selection ■Prioritise clinic visits Reliable Results ■Quantitative rapid test ■Excellent correlation with laboratory based tests ■Simple sample preparation minimises pre-analytical errors ■All components contained within each kit ■CE marked See what IBDoc can do for your patients Please visit to find out more. If you are interested in evaluation of IBDoc in your clinic please email

10 PERSPECTIVE 2019 The use of biochemical testing to support clinical decision making has grown extensively. However, in some hospitals certain analytes are still not routinely tested in-house. Patient samples are sent away to a referral laboratory for analysis or are stored and batch tested once or twice a week. This means that it can take several weeks before a result is available. Treatment decisions often have to be made without the benefit of the analyte information, or potentially more invasive and costly procedures must be performed to help determine the most appropriate course of action. In these situations Point-of-Care (POC) testing can add significantly to the management of patients. By streamlining the diagnostic process it enables rapid triage, helping to ensure appropriate, more timely treatment decisions are made. In addition to the healthcare benefits, POC testing also offers patients the benefit of direct discussion of test results with their clinician and the determination of an appropriate treatment plan. These factors can significantly relieve patient anxiety that delays from traditional laboratory testing can cause. Rapid Drug Monitoring Serum trough levels for biologics are extremely useful in determining effective treatment, as these compounds are prone to either a primary loss of response or a loss of response over time. Historically testing has been performed by ELISA methods which necessitate batch testing in order to be cost efficient. Batch testing inevitably introduces a delay in obtaining the result which is compounded by the fact that few hospitals run the analysis themselves – most use a referral service which can add further delays of up to several weeks. Consequently patients may have been administered multiple further drug doses before the delivery can be optimised into the therapeutic window. In a poster presented by C. Rentsch1 at ECCO 2018, 77% of patients required dose adjustment based on the serum trough levels achieved after the first dose, with 51% requiring dose reduction and 26% requiring dose escalation. In the absence of timely trough level information these patients are likely to receive subsequent doses without the appropriate adjustment therefore compounding the situation. Anti-TNFα POC The BÜHLMANN Quantum Blue® Infliximab and Adalimumab assays enable rapid, individual testing of serum samples to give trough level results in about an hour. This allows proactive management of patients through adjustment of the next dose to a more appropriate level. Obtaining rapid results for serum drug levels not only enables optimisation of treatment, minimising loss of response and side effects but also saves valuable healthcare resources. The Quantum Blue TDM assays are simple to run and are read using a small bench top device. They can be performed in the laboratory or infusion clinic to give quantitative results in around an hour. Studies have shown that the results using the rapid method are comparable to the traditional laboratory ELISA test result2,3. Tests can be performed in the laboratory, but when performed by nurses in the clinic they still have a good correlation to the laboratory result [Figure1]3 . The total test time is ~ 1 hour (actual assay time is 15 minutes). This offers the opportunity for patients to come to their appointment and have bloods taken for analysis by the nurse in the infusion clinic. They can wait for the results and have their next drug dose optimised based on the test data. Are You Fed-up Waiting for Results? Get Answers Faster with Point-of-Care Testing “[Quantum Blue] is a good alternative for the conventional ELISA method for the measurement of IFX serum concentrations at trough in IBD.2” Strik et al. “This rapid test strategy has the potential to reduce patient risks and improve patient outcomes without negative cost implications1” Rentsch et al. “The test can accurately be performed by a nurse which means that TDM now can be moved from a distant laboratory to the near patient facility like the infusion centre and ensure correct dosing in IBD and other patients on IFX treatment.3” Lindsjo et al. Quantum Blue® Infliximab / Lay-user (µg/ml) Reference Laboratory (NRD, µg/ml) Figure 1: Correlation of the results obtained with the QB-IFX rapid test done by a nurse and a lab person. r = 0.92, p < 0.001

Find out more at 11 Faecal Calprotectin POC Faecal calprotectin concentrations are widely acknowledged to correlate to the degree of mucosal inflammation in the gut. However, results are often not available at the point of decision making. A recent study by Derwa et al.4 regarding the factors effecting clinical decision making in IBD found that: ‘almost 60% of patients that were referred for investigation had no evidence of mucosal inflammation’ The study went on to conclude that: Rapid The BÜHLMANN Quantum Blue is a compact device that can be used in clinics or laboratories to give rapid quantitative results in just 15 minutes making results available to support the clinical decision making process. Accurate Numerous publications over the years have demonstrated the correlation of the result from the Quantum Blue assays to the health of the gut and the clinical outcome [Figure2]6. Standardised For over 10 years BÜHLMANN has specialised in calprotectin testing . It has the broadest range of faecal calprotectin assays available, providing assays for large central laboratories, smaller spoke laboratories, IBD clinics and for patient self-testing at home. Because the assays are all manufactured together they are all standardised, giving consistent results and cut-off values in the various locations [Figure 3]8. By working alongside traditional laboratory methods, POC testing can enhance the service that is provided by developing new pathways of care, supporting timely diagnosis, monitoring and treatment of patients. Flexible: All the Quantum Blue assays offer: ■ Single use tests: □ No need to batch samples □ Individually packaged test to maintain quality until use ■ Simple bench top reader (the size of a desk top telephone) □ Used as a stand-alone device or connected to a PC ■ Controls included within each kit ■ High correlation to traditional ELISA methods References: 1. C. Rentsch et al. Pharmacist-led proactive therapeutic drug monitoring with infliximab: utility of and cost-saving with the use of a rapid assay for assessing drug level. ECCO 2018. 2. A. Strik et al. Validation of the Quantum Blue Infliximab level rapid test in clinical practice of patients with inflammatory bowel disease. ECCO 2018. 3. I. Lindsjo et al. Patient-near infliximab trough- level testing by a novel quantitative rapid test: The Quantum Blue Infliximab test. UEGW 2016. 4. Y. Derwa et al. Factors affecting clinical decision- making in inflammatory bowel disease and the role of point-of-care calprotectin. Therap.Adv. Gastroenterol. 2018 Vol 11: 1-18 5. A. Moniuszko et al. Rapid fecal calprotectin test for prediction of mucosal inflammation in UC and CD: A prospective cohort study. Pol. Arch. Internal Med. 2017. 6. T. Lobaton et al. A new rapid test for faecal calprotectin predicts endoscopic remission and postoperative recurrence in Crohn’s disease. J of Crohn’s and Colitis 2013. 7. E. Abej et al. Utility of faecal calprotectin in the real-world clinical care of patients with inflammatory bowel disease. Can. J. Gastroenterol Hepatol.2016. 8. L. Coorevits et al. Faecal calprotectin: comparative study of the Quantum Blue rapid test and an established ELISA method. Clin Chem Lab Med 2012. Find out more at: See how point of care testing can impact patient care in your hospital. Contact us to request an evaluation: Email “This rapid bedside test can facilitate clinical decisions on hospital admission, such as deciding whether the IBD treatment should be intensified. Similarly, in the ambulatory setting, it is crucial when determining whether a patient should undergo endoscopy or not5” Moniuszko et al. “Introduction of routine pointof-care faecal calprotectin testing could, potentially, improve the appropriateness of clinical decisionmaking, streamline resource allocation, reduce adverse events associated with injudicious use of medications and reduce costs4” Derwa et al. “We observed that FC, measured both with fCAL ELISA and the rapid Quantum Blue, was able to discriminate between the different levels of endoscopic activity, as well as to detect the presence or absence of ulcer6” Lobaton et al. “We found that in a referral population of persons with IBD, positive fCAL was significantly associated with abnormal endoscopy, elevated serum CRP, low serum Hg, and low serum albumi7” Abej et al. Product Description Product Code Kit Size Faecal calprotectin standard range 30 - 300µg/g LF-CAL25 25 Faecal calprotectin high range 100 - 1800µg/g LF-CHR25 25 Faecal calprotectin extended range 30 – 1000µg/g LF-CALE25 25 Serum calprotectin 0.42 - 10µg/ml LF-MRP25 25 Ascites calprotectin 0.19 – 1.9µg/ml LF-ASC25 25 CRP 1-25mg/l LF-CRP25 25 Infliximab serum trough levels 0.4 - 20µg/ml (linear up to 180µg/ml) LF-TLIF25 25 LF-TLIF10 10 Adalimumab serum trough levels 1-35µg/ml LF-TLAD25 25 LF-TLAD10 10 The Quantum Blue reader can be used with a range of assays to give quantitative results in a time frame that can impact the clinical decision: Calprotectin, µg/g faeces Date Figure 3. Faecal calprotectin: comparative study of the Quantum Blue rapid test and an established ELISA method. Figure 2. FC-QPOCT (Quantum Blue fCAL) was also able to discriminate between the different grades of endoscopic activity.

12 PERSPECTIVE 2019 The FIT Revolution Coming to Your Practice Soon The initial aim was to test a minimum of 5500 patients in London, and further patients across the UK to create a robust evidence base that patients, GPs and hospital doctors can use with confidence. NHS England is funding the work through RM Partners and all hospitals that manage referrals for suspected colorectal cancer are eligible to join the study. When Alpha Laboratories previously reported on progress of the NICE FIT study (Focus on FIT 2018), 1000 patients had been recruited. Earlier this year Mr Muti Abulafi, consultant colorectal surgeon and chief investigator at Croydon University Hospital [Figure1], presented an update at the Royal College of Physicians with some of the interim results from the study. He reported that 12 months on, over 11,000 patients had now been recruited in sites right across England [Figure 2]. Although recruitment has now finished for the main study, there are still some sub-studies ongoing; a review of the patient and GP experience, a multi sampling study as well as an additional biomarker study. The presentation reviewed data from 4,069 patients with both FIT and colonoscopy results and where the clinical data had been thoroughly checked for correct coding of data entry. The number of cancers in this data set was 105 (2.5%) [Figure 3]. This interim data was similar in number to the 10 studies across two technologies that were reviewed by the NICE DG301 committee and used to generate their recommendation on the applications of FIT. Optimised Cut-Off of 2 µg Hb/g faeces Mr Abulafi presented a case that compared the NICE DG30 guideline cut-off of 10 µg Hb/g faeces where 94 out of the 105 cancers were positive, to an optimised cut-off of 2 µg Hb/g faeces where 101 out of 105 cancers were positive. Mr Abulafi suggested that identification of patients with cancer was a priority and hence FIT should be used as a rule in rather than the original NICE proposal of a rule out test. He suggested that using the test in this way would reduce missing cancer by two thirds. The NICE FIT Study is a research project in Bowel Cancer Care that has been initiated by the department of Colorectal Surgery at Croydon University Hospital together with RM Partners Accountable Cancer Network in South and West London. Evidence from studies conducted around the world indicate that faecal immunochemical testing (FIT) could rule out bowel cancer in symptomatic patients, thus avoiding the need for invasive and costly colonoscopy. Following a review of these studies, NICE1 in 2017 recommended using FIT in primary care for patients presenting to their GPs with low risk symptoms (cancer risk <3%) before referral to secondary care. However, there has never been a large research study on FIT published in England, that looks at faecal haemoglobin level variation by age, sex, ethnicity and deprivation. Large scale diagnostic studies are required to create reference values for the English population with the defined symptom spectrum recommended for referral under the NICE suspected cancer referral guidelines (NICE NG12 20152). The NICE FIT study is the largest study in England investigating whether FIT can be used as a triage tool in primary care to guide referrals for colonoscopy. Figure 2. As of February 2019, 11523 patients across England had been recruited to the NICE FIT Study Figure 1. Mr Muti Abulafi, (5th from the left) and his team at Croydon University Hospital.

Find out more about FIT at 13 The evidence that supports this proposal was then used to model what impact this would have on colonoscopy resources if a 2 µg Hb/g faeces cut-off was applied [Figure 4]. Mr Abulafi suggested that for every 1000 patients tested, 300 would be positive, of which 25 would have cancer (PPV 8%), 28 HRA and 35 IBD (PPV 28%) Of the 700 negative FIT results two will be missed cancers (NPV 99.8%). Safety Netting would result in additional secondary care referrals from this group. However it is estimated that the overall referrals for colonoscopy would result in a reduction between 30-50 % of the original 1,000. Of course there is still another 7,500 patient FIT and colonoscopy results yet to be reviewed. This would add to the statistical significance of the findings as in total it would double the data reviewed by NICE in 2017. However, the conclusion of the presentation suggested that there was definitely a revolution in progress with FIT. The early results have proved promising especially in view of the optimised cut-off of 2 µg Hb/g faeces proposed by Mr Abulafi for the symptomatic population, but that additional work on evidence base and safety netting pilots should be implemented to complete the proposed patient pathway. References 1. NICE DG30 (2017), Quantitative faecal immunochemical tests to guide referral for colorectal cancer in primary care. Section 4 – Evidence. chapter/4-Evidence 2. NICE NG12 (2015), Suspected cancer: recognition and referral. “FIT should be used as a rule in rather than the original NICE proposal of a rule out test. Using the test in this way would reduce missing cancer by two thirds.” Figure 3. Using the Limit of Detection as a cut-off threshold would reduce missing cancer by two thirds Figure 4. Using FIT to triage symptomatic patients could reduce colonoscopy requirements by 30-50% Alpha Laboratories is proud to be supporting the NICE FIT study by providing the FIT analyser (HM_JACKarc), the FIT kits, the raw materials and patient instruction leaflets. Expertise and experience in both the logistics and analysis of FIT specimens is provided by the team at the Bowel Cancer Screening Hub- South of England, led by Sally Benton [Figure 5]. The study team has created a website where full details can be found at Figure 5. Sally Benton (left) with staff at the Bowel Cancer Screening Hub - South of England