Original Title: Tests de porteur : choix des maladies, considérations et enjeux éthiques, psychosociaux, socioculturels, organisationnels et économiques

Authors' objectives: Carrier status screening allows for the identification of individuals who carry a known pathogenic genetic variant in a gene associated with an autosomal recessive genetic disease. To be affected by an autosomal recessive genetic disease, a child must inherit a pathogenic variant from each of their biological parents, meaning that both alleles of the gene are mutated in the child. A couple where both partners are carriers of variants in the same gene has a 25% probability of having a child affected by the disease they carry. The objective of carrier status screening is to provide partners in a reproductive project with information regarding their reproductive risks as a couple to allow them to make free and informed choices concerning their family planning. The ministère de la Santé et des Services Sociaux (MSSS) has asked the National Institute of Excellence in Health and Social Services (INESSS) to produce a state of knowledge report to specify the principles and criteria to be considered for evaluating the relevance of carrier status screening for autosomal recessive diseases. Various issues and considerations surrounding carrier status screening, including ethical, psychosocial, sociocultural, organizational, and economic issues, are also presented. This work is part of a broader mandate aimed at evaluating the relevance of adding certain diseases to the existing offer of carrier screening test in Quebec, which is the subject of separate reports.

Authors' results and conclusions: RESULTS (#1 INTERNATIONAL CARRIER STATUS SCREENING): The search of scientific and gray literature revealed carrier status screening strategies in place in twelve countries. Overall, carrier status screening strategies that exist internationally vary widely from one country to another. The variations concern the populations and diseases targeted by the screening as well as the funding of carrier test offers. In several countries, public and state-funded offers and programs are available primarily for individuals from certain ethnic groups who are considered to have a higher a priori risk for one or more recessive diseases. Cascade screening tests, based on family history, are state funded in several countries. (#2 CRITERIA AND PRINCIPLES TO CONSIDER FOR EVALUATING THE RELEVANCE OF CARRIER STATUS SCREENING FOR AUTOSOMAL RECESSIVE DISEASES): Four main criteria guiding the selection of diseases to be screened in a carrier status screening offer or program were identified. These are the frequency of carriers in the population, the severity of the disease, the genotype-phenotype correlation (the correlation between the gene and the disease), and the analytical validity of the screening test. Professional associations and working groups that have examined this issue have provided somewhat different recommendations, particularly regarding the criteria related to the frequency of carrier status and the severity of diseases. Regarding the criterion of carrier frequency, some professional associations have suggested threshold values for carrier status frequency ranging between 1 in 100 and 1 in 200, while other associations have recommended screening for the most frequent diseases in the population to allow for useful identification of carrier couples, without offering more specifics. Conversely, the Superior Health Council in Belgium mentions that carrier frequency should not play a decisive role, since screening for diseases with a low carrier rate could still lead to the identification of some carrier couples in the population. All professional associations and working groups have issued recommendations concerning the severity of diseases to be screened, with varying levels of detail. Some groups recommend screening for severe diseases that could have an impact on the reproductive plans of carrier couples. Other groups have provided more details on severity criteria, indicating, for example, that diseases should significantly reduce life expectancy and quality of life, have symptoms that appear from childhood, and cause intellectual or physical disabilities. Moreover, a majority of professional associations recommend that carrier status screening be offered to all individuals of reproductive age, in preconception or prenatal situations, regardless of their ethnicity. (#3 ETHICAL ISSUES SURROUNDING A CARRIER STATUS SCREENING TEST OFFER): Several ethical issues associated with carrier status screening have been identified in the literature. A first ethical issue is directly linked to the main objective of screening, for which there exists a tension between promoting reproductive autonomy and preventing the diseases targeted by the tests. An issue concerning the routinization of carrier status screening tests has also been raised, in which this screening could become a routine act in preconception or prenatal situations. The routinization of carrier screening tests could lead to increased social pressure to participate in screening and undermine the notion of informed consent. Carrier status screening performed through genetic tests also raises an issue of genetic selection. This issue is closely linked to the severity level of the diseases to be screened, and it can lead to problems of discrimination and stigmatization of individuals living with the diseases included in screening panels. Issues of equity in access to healthcare and insurability of participants who obtain a positive screening result have also been mentioned. (#4 COMMUNICATION WITH CANDIDATES FOR CARRIER STATUS SCREENING): Several pieces of information must be conveyed to individuals participating in carrier status screening to ensure they make a free and informed decision regarding their participation in the screening. The information to be provided includes notably the notion of optional participation in screening, basic principles of genetics, information on the diseases, the consequences when someone is identified as a carrier, the different test offers as well as their advantages and disadvantages. The various reproductive choices that can be considered following the identification of a carrier couple must also be discussed. The presentation of carrier status screening tests should ideally be done in the preconception period so that couples can benefit from a wider range of reproductive choices. (#5 IMPACT AND ISSUES OF A POSITIVE RESULT IN A CARRIER STATUS SCREENING TEST): A positive result also seems to be associated with a temporary increase in anxiety among individuals undergoing the test. However, this anxiety appears to have decreased in the months following the disclosure of results. Certain groups, including, notably, pregnant women and couples identified as carriers, seem to experience a higher level of anxiety following the announcement of a positive result regarding their carrier status. (#6 ORGANIZATIONAL AND ECONOMIC ISSUES RELATED TO CARRIER STATUS SCREENING TESTS): The organizational issues identified in the literature mainly concern the implementation of a carrier status screening program. Several organizational obstacles have been recognized by healthcare providers. These include, notably, the lack of genetic knowledge among practitioners and the population, as well as the lack of resources for practitioners and available time for disclosing results to concerned individuals. (#7 THE QUEBEC PERSPECTIVE ON CARRIER TESTING): The Quebec population seems very open to the various carrier tests offers, and would like more Quebecers to have access to them, and for a greater number of diseases. Eligibility criteria for the various carrier tests in place may limit access for people who don't know their family history or origins. According to the people surveyed, disease severity was an important factor in choosing which diseases to include in the test offers CONCLUSION: Overall, this state of knowledge has made it possible to determine the key issues and criteria to be considered for evaluating the relevance of carrier status screening for autosomal recessive diseases. These are summarized in Table 1.

Authors' methods: A search of scientific and gray literature was conducted in several databases without limitations regarding study designs. The selected studies had to focus on carrier status screening for autosomal recessive diseases offered in preconception or prenatal situations.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/fileadmin/doc/INESSS/Rapports/Depistage/INESSS_Statut_porteur_EC.pdf

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/fileadmin/doc/INESSS/Rapports/Depistage/INESSS_Statut_porteur_EC.pdf

English language abstract: An English language summary is available

Publication Type: Not Assigned

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)