Identifying the Optimum Strategy for Identifying Adults and Children With Celiac Disease: A Cost-Effectiveness and Value of Information Analysis.

OBJECTIVES: Celiac disease (CD) is thought to affect around 1% of people in the United Kingdom, but only approximately 30% are diagnosed. The aim of this work was to assess the cost-effectiveness of strategies for identifying adults and children with CD in terms of who to test and which tests to use. METHODS: A decision tree and Markov model were used to describe testing strategies and model long-term consequences of CD. The analysis compared a selection of pre-test probabilities of CD above which patients should be screened, as well as the use of different serological tests, with or without genetic testing. Value of information analysis was used to prioritize parameters for future research. RESULTS: Using serological testing alone in adults, immunoglobulin A (IgA) tissue transglutaminase (tTG) at a 1% pre-test probability (equivalent to population screening) was most cost-effective. If combining serological testing with genetic testing, human leukocyte antigen combined with IgA tTG at a 5% pre-test probability was most cost-effective. In children, the most cost-effective strategy was a 10% pre-test probability with human leukocyte antigen plus IgA tTG. Value of information analysis highlighted the probability of late diagnosis of CD and the accuracy of serological tests as important parameters. The analysis also suggested prioritizing research in adult women over adult men or children. CONCLUSIONS: For adults, these cost-effectiveness results suggest UK National Screening Committee Criteria for population-based screening for CD should be explored. Substantial uncertainty in the results indicate a high value in conducting further research.

Create to Collaborate: using creative activity and participatory performance in online workshops to build collaborative research relationships.

BACKGROUND: Creative methods/practices have been highlighted as helpful to develop more collaborative, equitable research partnerships between researchers and communities/public-participants. We asked artist partners to design four online workshops, one on each research priority area: school environments and mental health; wellbeing within the Somali community; air pollution; health data. We aimed to understand whether creative processes can enable public-participants and researcher- participants to meet in a neutral space to discuss a research theme and begin to build collaborative relationships through more equal engagement. Ideas could be taken forwards with seed funding, providing opportunity for collaboration to continue beyond initial workshops. METHODS: Different artist partners designed and facilitated four workshops. Evaluation data was collected on each workshop using participatory observation and fieldnotes, alongside chatlog data, and one-to-one interviews with 21 workshop participants, providing a contextually rich, comparative evaluation across four diverse workshops. Analysis was thematically driven. RESULTS: Artist partners took different approaches to designing workshops. The workshops began with introductory games and activities, and there was less emphasis on introductions of people's roles, with the intention to avoid hierarchical dynamics. Whilst public-participants enjoyed this, some researchers found it challenging and reported confusions over their workshop roles. Disrupting usual practice and challenging norms was not always an easy experience. There were examples where emergent, co-created knowledge was enabled. However, it was more challenging to facilitate longer-term collaborative research projects from the workshops due to different stakeholder priorities, and lack of staff time/ less sense of ownership for further work. CONCLUSIONS: Creative activities can influence and impact the types of conversations between public-participants and researchers in a way that changes and challenges power dynamics, shifting towards public-participant driven discussion. Whilst deconstructing hierarchies is important, supporting researchers is key so that any discomfort can be productive and experienced as a vital part of co-production. Longer term collaborative research projects were limited, highlighting a need for facilitation beyond initial workshops, and a sense of ownership from workshop participants to take things forwards. Workshops like these may lend themselves well to research prioritisation. However, taking community-led ideas forwards within research funding landscapes remains challenging.

Create to Collaborate aimed to develop and facilitate creative public involvement workshops with members of the public, researchers, and community organisations, who were potentially interested in collaborating on a future health research project. We wanted to evaluate the extent to which creative, external facilitation by different artists could enable the development of more equal relationships and reduce power differences at the beginning of a research process. We worked with artists who designed and facilitated an online workshop, and community partners who helped recruit members of the public to increase diversity in participation. Then, we delivered and evaluated the workshops to understand different participants' experiences. Four workshops are reported in this article, each focused on a different topic: mental health in school environments, wellbeing in Bristol's Somali community, air pollution, and health data. We took observational notes at the workshops and conducted one-to-one qualitative interviews with 21 workshop participants. Feedback from public-participants taking part in creative workshops led by artist facilitators described them as 'engaging', 'comfortable' and 'equitable'. Researcher-participants reported workshops as 'open', 'inclusive' and 'engaging', whilst also reporting some confusion over what their own roles were and how much they could contribute as academic researchers. The project demonstrates a need for further clarity, particularly for researchers, over what roles may be in setting up a collaborative relationship, and possible disparity in expectations between those attending in an employment capacity and those joining as a public-participant in their own time.

Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling.

BACKGROUND: Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to have a diagnosis. Untreated coeliac disease may lead to malnutrition, anaemia, osteoporosis and lymphoma. OBJECTIVES: The objectives were to define at-risk groups and determine the cost-effectiveness of active case-finding strategies in primary care. DESIGN: (1) Systematic review of the accuracy of potential diagnostic indicators for coeliac disease. (2) Routine data analysis to develop prediction models for identification of people who may benefit from testing for coeliac disease. (3) Systematic review of the accuracy of diagnostic tests for coeliac disease. (4) Systematic review of the accuracy of genetic tests for coeliac disease (literature search conducted in April 2021). (5) Online survey to identify diagnostic thresholds for testing, starting treatment and referral for biopsy. (6) Economic modelling to identify the cost-effectiveness of different active case-finding strategies, informed by the findings from previous objectives. DATA SOURCES: For the first systematic review, the following databases were searched from 1997 to April 2021: MEDLINE® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), Cochrane Library, Web of Science™ (Clarivate™, Philadelphia, PA, USA), the World Health Organization International Clinical Trials Registry Platform ( WHO ICTRP ) and the National Institutes of Health Clinical Trials database. For the second systematic review, the following databases were searched from January 1990 to August 2020: MEDLINE, Embase, Cochrane Library, Web of Science, Kleijnen Systematic Reviews ( KSR ) Evidence, WHO ICTRP and the National Institutes of Health Clinical Trials database. For prediction model development, Clinical Practice Research Datalink GOLD, Clinical Practice Research Datalink Aurum and a subcohort of the Avon Longitudinal Study of Parents and Children were used; for estimates for the economic models, Clinical Practice Research Datalink Aurum was used. REVIEW METHODS: For review 1, cohort and case-control studies reporting on a diagnostic indicator in a population with and a population without coeliac disease were eligible. For review 2, diagnostic cohort studies including patients presenting with coeliac disease symptoms who were tested with serological tests for coeliac disease and underwent a duodenal biopsy as reference standard were eligible. In both reviews, risk of bias was assessed using the quality assessment of diagnostic accuracy studies 2 tool. Bivariate random-effects meta-analyses were fitted, in which binomial likelihoods for the numbers of true positives and true negatives were assumed. RESULTS: People with dermatitis herpetiformis, a family history of coeliac disease, migraine, anaemia, type 1 diabetes, osteoporosis or chronic liver disease are 1.5-2 times more likely than the general population to have coeliac disease; individual gastrointestinal symptoms were not useful for identifying coeliac disease. For children, women and men, prediction models included 24, 24 and 21 indicators of coeliac disease, respectively. The models showed good discrimination between patients with and patients without coeliac disease, but performed less well when externally validated. Serological tests were found to have good diagnostic accuracy for coeliac disease. Immunoglobulin A tissue transglutaminase had the highest sensitivity and endomysial antibody the highest specificity. There was little improvement when tests were used in combination. Survey respondents (n = 472) wanted to be 66% certain of the diagnosis from a blood test before starting a gluten-free diet if symptomatic, and 90% certain if asymptomatic. Cost-effectiveness analyses found that, among adults, and using serological testing alone, immunoglobulin A tissue transglutaminase was most cost-effective at a 1% pre-test probability (equivalent to population screening). Strategies using immunoglobulin A endomysial antibody plus human leucocyte antigen or human leucocyte antigen plus immunoglobulin A tissue transglutaminase with any pre-test probability had similar cost-effectiveness results, which were also similar to the cost-effectiveness results of immunoglobulin A tissue transglutaminase at a 1% pre-test probability. The most practical alternative for implementation within the NHS is likely to be a combination of human leucocyte antigen and immunoglobulin A tissue transglutaminase testing among those with a pre-test probability above 1.5%. Among children, the most cost-effective strategy was a 10% pre-test probability with human leucocyte antigen plus immunoglobulin A tissue transglutaminase, but there was uncertainty around the most cost-effective pre-test probability. There was substantial uncertainty in economic model results, which means that there would be great value in conducting further research. LIMITATIONS: The interpretation of meta-analyses was limited by the substantial heterogeneity between the included studies, and most included studies were judged to be at high risk of bias. The main limitations of the prediction models were that we were restricted to diagnostic indicators that were recorded by general practitioners and that, because coeliac disease is underdiagnosed, it is also under-reported in health-care data. The cost-effectiveness model is a simplification of coeliac disease and modelled an average cohort rather than individuals. Evidence was weak on the probability of routine coeliac disease diagnosis, the accuracy of serological and genetic tests and the utility of a gluten-free diet. CONCLUSIONS: Population screening with immunoglobulin A tissue transglutaminase (1% pre-test probability) and of immunoglobulin A endomysial antibody followed by human leucocyte antigen testing or human leucocyte antigen testing followed by immunoglobulin A tissue transglutaminase with any pre-test probability appear to have similar cost-effectiveness results. As decisions to implement population screening cannot be made based on our economic analysis alone, and given the practical challenges of identifying patients with higher pre-test probabilities, we recommend that human leucocyte antigen combined with immunoglobulin A tissue transglutaminase testing should be considered for adults with at least a 1.5% pre-test probability of coeliac disease, equivalent to having at least one predictor. A more targeted strategy of 10% pre-test probability is recommended for children (e.g. children with anaemia). FUTURE WORK: Future work should consider whether or not population-based screening for coeliac disease could meet the UK National Screening Committee criteria and whether or not it necessitates a long-term randomised controlled trial of screening strategies. Large prospective cohort studies in which all participants receive accurate tests for coeliac disease are needed. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019115506 and CRD42020170766. FUNDING: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 44. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Around 1 in 100 people in the UK has coeliac disease. It develops when the immune system attacks the lining of the gut after eating gluten. It is thought that only one in three people with coeliac disease is currently diagnosed. Without treatment, people with coeliac disease are at an increased risk of anaemia, osteoporosis and cancer. Treatment is a lifelong gluten-free diet. Diagnosing coeliac disease is difficult. Some people have minimal or non-specific symptoms, such as pain, indigestion or bloating, so knowing who to test is tricky. WHAT DID WE DO?: We wanted to establish who should be tested for coeliac disease, what tests should be used and whether or not invasive testing (a gut biopsy) is necessary for everyone. We looked at existing studies and data from general practices, and conducted an online survey, and brought everything together in an economic (cost) analysis. WHAT DID WE FIND?: Using individual symptoms is not helpful to identify people who may have coeliac disease. People with coeliac disease are more likely to have a combination of symptoms. People with anaemia, type 1 diabetes, osteoporosis, thyroid disorders, immunoglobulin A deficiency, Down syndrome, Turner syndrome or a family history of coeliac disease are more likely to have coeliac disease and should be offered tests. Common blood tests for coeliac disease are very accurate, particularly when used in combination with genetic testing. Blood tests alone can be used for diagnosis for some people. Others will need a biopsy to confirm the diagnosis. Whether or not this is needed depends on their risk of coeliac disease: whether or not they have symptoms and whether or not they have a condition that puts them at higher risk. Shared decision-making is important for individuals considering an invasive test, depending on how certain they want to be about their diagnosis before starting a gluten-free diet.

Accuracy of potential diagnostic indicators for coeliac disease: a systematic review protocol.

INTRODUCTION: Coeliac disease (CD) is a systemic immune-mediated disorder triggered by gluten in genetically predisposed individuals. CD is diagnosed using a combination of serology tests and endoscopic biopsy of the small intestine. However, because of non-specific symptoms and heterogeneous clinical presentation, diagnosing CD is challenging. Early detection of CD through improved case-finding strategies can improve the response to a gluten-free diet, patients' quality of life and potentially reduce the risk of complications. However, there is a lack of consensus in which groups may benefit from active case-finding. METHODS AND ANALYSIS: We will perform a systematic review to determine the accuracy of diagnostic indicators (such as symptoms and risk factors) for CD in adults and children, and thus can help identify patients who should be offered CD testing. MEDLINE, Embase, Cochrane Library and Web of Science will be searched from 1997 until 2020. Screening will be performed in duplicate. Data extraction will be performed by one and checked by a second reviewer. Disagreements will be resolved through discussion or referral to a third reviewer. We will produce a narrative summary of identified prediction models. Studies, where 2×2 data can be extracted or reconstructed, will be treated as diagnostic accuracy studies, that is, the diagnostic indicators are the index tests and CD serology and/or biopsy is the reference standard. For each diagnostic indicator, we will perform a bivariate random-effects meta-analysis of the sensitivity and specificity. ETHICS AND DISSEMINATION: Results will be reported in peer-reviewed journals, academic and public presentations and social media. We will convene an implementation panel to advise on the optimum strategy for enhanced dissemination. We will discuss findings with Coeliac UK to help with dissemination to patients. Ethical approval is not applicable, as this is a systematic review and no research participants will be involved. PROSPERO REGISTRATION NUMBER: CRD42020170766.