Original Title: Utilisation judicieuse des analyses de biologie médicale pour le diagnostic et le suivi du traitement d’une infection à Helicobacter pylori

Authors' objectives: Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the inner lining of the stomach. The infection causes gastric inflammation and plays a role in the onset of dyspepsia, the development of peptic ulcers and gastric cancers (adenocarcinomas and mucosa-associated lymphoid tissue [MALT] lymphomas). The World Health Organization has classified H. pylori as a type 1 carcinogen. In Quebec, three medical biology tests, listed in the Répertoire québécois et système de mesure des procédures de biologie médicale, enable non-invasive identification of H. pylori infection: the carbon-13-labeled urea breath test, the stool antigen test, and the serological test. The ministère de la Santé et des Services sociaux has asked the Institut national d'excellence en santé et en services sociaux (INESSS) to conduct an assessment to provide scientific and clinical insight into the diagnostic value, clinical usefulness and issues associated with the various medical biology tests used to identify H. pylori infection, and to formulate recommendations on the stool antigen test service offering and the situations in which the various non-invasive tests are indicated. This work is being conducted in a context where issues of accessibility to the non-invasive tests recommended in clinical practice guidelines are being raised, as well as an apparent misuse of the serological test.

Authors' results and conclusions: RESULTS (#1 INITIAL DIAGNOSIS AND FOLLOW-UP OF INFECTION ERADICATION BASED ON TESTS CAPABLE OF DETECTING ACTIVE INFECTION): The overall prevalence of H. pylori infection is low in Quebec (13%), but higher in indigenous communities, and among people born in South America, Africa, and Asia. • Untreated H. pylori infection can lead to acute gastritis, which usually becomes chronic and may progress to gastric cancer. • The stool antigen test and the 13C-urea breath test can detect an active infection, whereas the serological test does not distinguish between a resolved past infection and an active one. n Quebec, for the year 2022-2023, serological testing was prescribed almost 20 times more often than the 13C-urea breath test, and close to 5 times more often than the stool antigen test, despite the fact that serological testing is not generally recommended in clinical practice guidelines. However, according to the latest data from 2023-2024, a replacement trend of serological testing by stool antigen testing is observed. Thus, serological tests have been prescribed 11 times more often then the 13C-urea breath test and 1,5 times more often than the stool antigen test. (#2 IMPROVING KNOWLEDGE FOR JUDICIOUS USE OF NON-INVASIVE TESTS AND OPTIMIZATION OF THE DIAGNOSTIC TRAJECTORY) : Lack of knowledge about the non-invasive tests available, and the limitations of each, are barriers to their judicious use. Biomedical requisition forms generally do not include either the H. pylori-specific stool antigen test or the 13C-urea breath test among the available options - usually only the serological test is proposed. (#3 BARRIERS TO BE OVERCOME TO FACILITATE ACCESS TO NON-INVASIVE TESTS): Access to non-invasive tests varies between facilities and regions: – for the 13C-urea breath test, samples can be taken in any hospital in Quebec. However, sample analysis is offered only at the CHUM, which accepts all requests from the SIL-P or from a centre that has an agreement with the CHUM; – stool antigen testing is performed in the vast majority of laboratory clusters; – serological testing is available in all regions. • Stool samples for antigen testing are collected by self-collection, and unlike other non-invasive tests, do not require human resources: – sampling for the 13C-urea breath test is conducted by staff at the specimen collection centre (nursing assistant, nurse or medical technologist) - the test takes around 40 minutes; – sampling for the serological test is conducted at a specimen collection centre by a phlebotomist. (#4 DELAYS TO BE EXPECTED BEFORE CHANGES IN PRACTICE ARE OBSERVED): The bidding process by laboratories to procure stool antigen test kits may lead to delays in the roll out of the test and require adjustments depending on the bids accepted (some of which may involve the purchase of equipment, including devices). • The validation process for stool antigen testing in laboratories where the test is not already implemented may take some time. (#5 ENVIRONMENTAL CONSIDERATIONS FOR THE COMMON GOOD): Using a locally available test helps reduce greenhouse gas emissions resulting from the transportation of samples. • Wisely prescribing a non-invasive test in the right clinical situation contributes to an ecologically sustainable healthcare system, notably by limiting the need for other confirmatory tests.

Authors' recommendations: In light of all the information gathered, and in such a way as to cover the five dimensions of the INESSS Statement of Principles and Ethical Foundations (populational, clinical, organizational, economic, and sociocultural dimensions), proposed recommendations were first formulated with the members of the Advisory Committee, then presented to the members of the Permanent Deliberative Committee - Diagnostic Approaches and Screening. At the end of the discussions and deliberations, the members of the Permanent Deliberative Committee proposed certain modifications to the wording, which were incorporated by the INESSS into the final formulations. These were unanimously endorsed by all members of the Permanent Deliberative Committee. In summary, from a clinical point of view, all committee members were of the opinion that the stool antigen test and the 13C-urea breath test should be the tests of choice since they can identify active H. pylori infection. It has been pointed out by some that, although serological testing should not be used to initiate or follow up treatment, it could be useful in certain clinical situations to exclude, for example, an infection in the presence of an uncertain clinical picture, or if the person is taking proton pump inhibitors that cannot be discontinued. These opinions are based in particular on the high negative predictive value and low prevalence of H. pylori infections in Quebec. According to the majority of members, it is important to maintain a certain supply of serological tests. However, treatment should not be based on a positive serological test result - a confirmatory test, such as the stool antigen test or the 13C-urea breath test, would then be desirable, otherwise people risk receiving unnecessary treatments with the associated undesirable side effects. From an organizational point of view, the entire Permanent Deliberative Committee supported the fact that stool antigen testing should be offered in at least one laboratory in each of the laboratory clusters, to cover all of Québec. Committee members did, however, identify and acknowledge certain issues and limitations associated with the broader offering of stool antigen testing, including regulatory issues (e.g., assay validation, kit bidding) that could impede the implementation of stool antigen testing. Committee members also pointed out that the purchase of analyzers could be required in some laboratories, depending on the volume of analyses, if stool antigen testing is implemented on a large scale in Quebec. Should the need arise to acquire automated analyzers for certain laboratories, the cost would be between $100,000 and $200,000 per device. The committee as a whole was of the opinion that there is a need for training for personnel involved in sampling for the 13C-urea breath test at sampling centres. The committee also recognized the importance of structuring the dissemination and communication process with professional orders, federations, and associations, in order to promote the clinical tool on the optimal use of diagnostic tests and treatments for H. pylori infection, to be produced by the INESSS in 2024. (#1 RECOMMENDATIONS FOR THE JUDICIOUS USE OF NON-INVASIVE TESTS LISTED IN THE RÉPERTOIRE): The stool antigen test or the 13C-urea breath test should be the preferred tests for the detection of active H. pylori infection or monitoring of its eradication. The following situations may justify the use of serological testing: • if neither the stool antigen test nor the 13C-urea breath test is available; • if, for clinical reasons, neither the stool antigen test nor the 13C-urea breath test can be prescribed. Serological testing should not be used for treatment follow-up. (#2 RECOMMENDATIONS REGARDING ACCESS TO TESTING FOR ACTIVE H. PYLORI INFECTION AND FACILITATION OF IMPLEMENTATION OF PROPOSED CHANGES): All laboratory clusters should roll out the stool antigen test (code 40005) to make it available to the population they serve, notably for high-volume facilities expressing the need. To monitor implementation of the stool antigen test, laboratory clusters should develop and standardize information on request forms to include a field reserved for this test for H. pylori. Depending on the development of stool antigen testing and the residual volume of serological tests, centres dedicated to serological testing could be considered. Each laboratory cluster should develop and implement ways to: • operationalize the implementation of the indications of clinical relevance recommended by the INESSS as a framework for the use of H. pylori-specific serological testing; • inform requesters of the reasons justifying refusal of the serological test in the report, where applicable. (#3 RECOMMENDATIONS FOR ENHANCING PRACTICES AND GENERAL KNOWLEDGE OF H. PYLORI INFECTION FOR INITIAL DIAGNOSIS AND TREATMENT FOLLOW-UP): The Centre hospitalier de l'Université de Montréal could develop an easily accessible, userfriendly Web-based training course on the sampling procedure for the 13C -urea breath test. Recommendations for the judicious use of non-invasive tests to detect H. pylori infection and verify its eradication should be the subject of a structured dissemination and communication process with professional orders, federations, and associations, as well as in academic institutions. In addition, a clinical tool formulating recommendations on the appropriate use of diagnostic tests and treatments for H. pylori infection should be developed and widely disseminated among the various circles concerned (work in progress by the INESSS - publication scheduled for 2024). (#4 RECOMMENDATION FOR FOLLOW-UP ON MEASURES TO OPTIMIZE THE USE OF NONINVASIVE TESTS FOR H. PYLORI): Measures to optimize the use of non-invasive tests for H. pylori could be monitored over a three-year period, to assess the impact of the proposed changes on the volume and associated costs of the medical biology analyses involved. CONCLUSION: The changes proposed in this report should help to enhance the quality of the diagnostic and follow-up trajectory, in line with best practices, and promote consistency between establishments across the province in terms of the services offered for the various tests. The changes in practice that may result from the present work will depend, however, on the dissemination and implementation of the recommendations in the various Quebec healthcare establishments and laboratories, as well as by the ministère de la Santé et des Services sociaux. The development of the future clinical tool by the INESSS and its planned dissemination in 2024 will consolidate knowledge of the various non-invasive tests available, support healthcare professionals involved in the diagnosis and management of H. pylori infection and promote practice harmonization across the province.

Authors' methods: The evaluation questions for this work were formulated to meet the objectives of the mandate, and to cover the five dimensions of the INESSS Statement of Principles and Ethical Foundations (populational, clinical, organisational, economic and sociocultural dimensions). In collaboration with a scientific information consultant (librarian), a systematic search of the scientific literature was conducted to document the clinical and economic dimensions in the MEDLINE, Embase, and EBM Reviews databases (Cochrane Database of Systematic Reviews, Health Technology Assessment, NHS Economic Evaluation Database). A manual search of the grey literature was also conducted, consulting, among others, the websites of learned societies specializing in the field related to the theme of the work, as well as regulatory, public health or health technology assessment agencies. The bibliographic references of the selected publications were also consulted to identify other relevant documents, including systematic reviews in support of the recommendations published in the clinical practice guidelines. Document selection and methodological quality assessment were conducted independently by two scientific professionals. Extraction, analysis, and synthesis of the information gathered were conducted by one professional, then validated by a second. The monographs of commercially available kits in Canada were consulted, and their medical device licence status was verified using Health Canada's MDALL application. To document the populational, sociocultural, and organizational dimensions, a manual search of the grey literature was conducted by consulting the websites of federal, provincial, and territorial governments, of groups, communities of practice or learned societies specializing in the field, or those of Quebec associations, federations, and professional orders involved in this work. Health data and statistics specific to Quebec and Canada were sought, notably through clinical-administrative databases, registries, or documents published by organizations that compile them. The efficiency of the interventions was assessed through a critical analysis of the economic literature, based on economic information relevant to the Quebec context. A budget impact analysis was conducted, using data from the latest complete financial years available at the time the work was done (fall-winter 2023-2024), taking into account the costs associated with the judicious use of the procedures of interest. Stakeholder perspectives were gathered through an Advisory Committee made up of healthcare professionals from various specialties and areas of expertise. Deliberation on the recommendations, based on an assessment of all the evidence and taking into account the five dimensions, was conducted with the members of the Permanent Deliberative Committee - Diagnostic Approaches and Screening. Finally, the overall quality of the work, its acceptability, and applicability were assessed by two external readers specializing in the field of interest.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/infection-a-helicobacter-pylori.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/infection-a-helicobacter-pylori.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)