RESUMO
MANDAT: L'Institut national d'excellence en santé et en services sociaux (INESSS) a reçu le mandat de la Direction de la biovigilance et de la biologie médicale (DBBM) du ministère de la Santé et des Services sociaux (MSSS) de réévaluer la pertinence de l'introduction des technologies de réduction des agents pathogènes (TRP) InterceptMC et MirasolMC pour le traitement des produits sanguins labiles au Québec. Il s'agit de la deuxième évaluation de ces technologies par l'INESSS à la suite de la recommandation en 2017 de ne pas introduire le procédé InterceptMC dans la chaîne de production des produits sanguins labiles au Québec. DESCRIPTION: Les TRP InterceptMC et MirasolMC sont des processus qui visent à inactiver certains virus, parasites et bactéries par l'utilisation d'agents chimiques ou physiques. Contrairement aux produits sanguins stables, les produits sanguins labiles (culots globulaires, plasma et plaquettes) offerts au Québec ne sont actuellement pas soumis à un tel processus. Advenant leur introduction, ces technologies pourraient s'ajouter aux
MANDATE: The Institut national d'excellence en santé et en services sociaux (INESSS) was mandated by the Direction de la biovigilance et de la biologie médicale (DBBM) of the Ministère de la Santé et des Services sociaux (MSSS) to reassess the relevance of introducing InterceptTM and MirasolTM pathogen reduction technologies (PRTs) for the treatment of labile blood products in Quebec. This is the second assessment of these technologies by INESSS following the recommendation in 2017 not to introduce the InterceptTM Blood System in the labile blood products' production chain in Quebec. DESCRIPTION: Intercept™ and Mirasol™ are PRTs that aim to inactivate certain viruses, parasites, and bacteria through the use of chemical or physical agents. Unlike stable blood products, labile blood products (packed red blood cells, plasma, and platelets) offered in Quebec are not currently subjected to such a process. If introduced, these technologies could be added to the various preventive measures that are already being used to reduce the risks of contamination. ASSESSMENT PROCESS: The assessment used an approach based on the overall value appraisal that the Institute advocates in its Statement of Principles and ethical fondations. A rapid review of the literature was carried out in order to mobilize evidence and reassess the relevance of introducing PRTs in the labile blood products' production chain in Québec. PRT manufacturers were invited to transmit relevant information. Contextual and experiential data was collected from stakeholders through a meeting with Héma-Québec, an expert advisory committee, a focus group with representatives of patient organizations, and a citizen panel. A budget impact analysis (BIA) aiming to quantify the expected financial impact following the introduction of a PRT for the treatment of plasma and platelets was also conducted. The comprehensive scientific, contextual, and experiential data was interpreted using a multidimensional framework to guide certain consultation processes as well as the deliberation process for the development of recommendations by the "Comité délibératif permanent - Remboursement et accès". Socio-CULTURAL DIMENSION: Héma-Québec deploys the preventive measures it deems necessary to ensure the safety of labile blood products distributed in Quebec. Similarly, the Canadian Blood Services (CBS) is implementing preventive measures for the other Canadian provinces and has gradually been rolling out PRTs since January 2022 for the treatment of platelet units in selected hospitals. Some countries that are socially and economically comparable to Canada have taken divergent positions on PRTs, with some being favourable, such as France and Switzerland, and others being unfavourable, such as England. Considering a partial or complete introduction in other countries and Canadian provinces and based on the precautionary principle, the Comité de biovigilance decided that it would be important to consider a strategic introduction of PRTs in order to prepare for the emergence of various pathogens in Quebec. However, the committee has specified that this technology should not replace current preventive measures and should apply only to a small percentage of labile blood products. Although Héma-Québec deems the infectious risks associated with labile blood products to be minimal, it considers the risks associated with the emergence of known pathogen agents (KPAs) and unknown pathogen agents (UPAs) to be legitimate and it regards PRTs as an insurance policy against these intangible and unpredictable risks. Moreover, following the Coronavirus Disease 2019 (COVID-19) pandemic, the potential risk of an emerging pathogen has become more apparent according to the representatives of patient associations that we consulted. Despite the transfusion safety measures in place for labile blood products, this awareness may, for some, have influenced their risk perception. POPULATION DIMENSION: Transfusion safety is a shared responsibility between Héma-Québec, which ensures the safety of blood products, and transfusion hospitals, which are responsible for the quality of the transfusion procedure for patients. Héma-Québec receives nearly 800 orders of labile blood products daily and delivers more than 295,000 of these products annually to hospital centres. Only plasma and platelet units, which represent 22% of the labile blood products distributed, could potentially be treated by PRTs. In order to meet transfusion safety needs, the blood system in Quebec could benefit from better communication on transfusion complications, more preventive measures for noninfectious complications, alternative treatments to transfusions, and increased selfsufficiency in labile blood products. Since the risk of infectious complications associated with transfusions is currently considered low and acceptable by all stakeholders consulted, the main benefit of a PRT occurs during the hypothetical emergence of an UPA. CLINICAL DIMENSION: Intercept™ and Mirasol™ technologies have been shown to be effective on a wide range of viruses, bacteria, and protozoa in laboratory tests. However, the effectiveness of these two PRTs is limited against certain spores, biofilms, residual endotoxins, prions, multidrug-resistant Gram-negative bacteria, and non-enveloped viruses. In addition, there are concerns about the lack of efficacy of Mirasol™ technology against blood-borne viruses such as hepatitis B and cytomegalovirus (CMV). The effects of Intercept™ and Mirasol™ technologies on the biological properties of platelets or plasma are considered acceptable. Both technologies have no effect on bleeding or haemostatic function. However, treatment with both PRTs is accompanied by a statistically significant decrease in post-transfusion platelet recovery, a decrease in the time interval between transfusions, and a statistically significant increase in the number of transfusions per patient. Finally, some studies report a statistically significant increase in the number of transfusion-refractory patients and an increase in alloimmunization rates for platelets treated with Intercept™ compared to conventional platelets. Long-term toxicity or oncogenicity associated with residual amotosalen is also a concern for the Intercept™ technology, especially in pediatrics. ORGANIZATIONAL DIMENSION: Héma-Québec is facing supply chain challenges due to an increase in demand, a constrained pool of donors and a limited shelf life for labile products. PRTs have the potential to reduce the time it takes to make certain labile blood products available if they are accompanied by the withdrawal of bacterial testing. However, compared to untreated products, PRTs lead to an increase in the frequency and number of transfusions per patient, which can thus affect blood product stocks. However, uncertainty remains as to the actual impact of PRTs on plasma or platelet stocks. Moreover, the introduction of these technologies would require changes in the production chain, such as the rapid treatment of collected blood products. According to HémaQuébec, the scale of these changes as well as the resources mobilized would be limited. CBS has made the decision to remove bacterial screening and irradiation from the production chain of products treated with Intercept™ in other Canadian provinces. However, in Quebec, the withdrawal of certain preventive measures that have shown their effectiveness in ensuring the safety of labile products is not unanimous and is not planned by Héma-Québec in the short term. ECONOMIC DIMENSION: A scientific literature update on economic efficiency identified one recently published study specifically assessing Intercept™. According to this analysis, the use of a PRT would have an incremental cost-utility ratio (ICUR) of $9.3 million per QALY gained compared to current preventive measures. This ICUR could see a downturn in the event of the emergence of an UPA, decreasing to $8.6M or approximately $331K per QALY earned, depending on scenario analyses based on rates of infectious transmission of previous pathogens. The conclusions established in the 2017 assessment by INESSS remain unchanged. Uncertainty remains as to the system's willingness to pay for a health intervention such as a PRT according to an insurance principle. Regarding the budgetary impact estimated by INESSS, the uncertainty surrounding certain BIA parameters, in particular the introduction strategy, supported a scenariobased approach. INESSS estimates that the introduction of a PRT to treat only 10% of platelet units, in a partial introduction scenario, would generate a net budget impact of $11.6 million over 10 years. The net budgetary impact is estimated at $157.4 million over 10 years when it is assumed that PRT would treat 100% of platelets and plasma. INESSS Recommendation: Based on the information available to date and given the importance of the uncertainties raised about the added value of PRTs in the production chain of labile blood products in Quebec, INESSS considers that it would not be fair and equitable to implement such a technology. INESSS may reassess the available PRTs, at the request of the Ministère de la Santé et des Services sociaux (MSSS), when new information likely to influence the recommendation becomes available