Original Title: Avis: pertinence de l’introduction d’un procédé d’inactivation des pathogènes pour les produits sanguins labiles au Québec

Authors' objectives: Pathogen inactivation in blood products refers to processes aimed at inactivating certain bacteria, viruses and parasites through the use of chemical or physical agents. Unlike stable blood products, the labile blood products (packed red blood cells, plasma and platelets) available in Quebec are not currently subjected to a pathogen inactivation process. Different preventive measures are, however, used to reduce the risk of contamination. Different photochemical pathogen inactivation methods for labile blood products have been developed in the past few years, such as the Intercept Blood System process (Cerus Corporation), which was recently approved by Health Canada. This technology offers the theoretical advantage of protecting against possible emerging pathogens, in addition to reducing the risk of infection by currently known pathogens. The MSSS asked INESSS to produce a report on the relevance of introducing this photochemical pathogen inactivation process into the production of its labile blood products in the Quebec context.

Authors' results and conclusions: RESULTS: (CURRENT SITUATIONS IN QUÉBEC) Héma-Québec is responsible for the province’s blood supply. It distributes more than 485,000 units of labile blood products annually. These products include packed red blood cells, platelets and plasma. Since photochemical pathogen inactivation technologies for red blood cells and whole blood are still under clinical development, only platelets and plasma, which account for 25% of the transfusion needs, could be treated in the short term. The risks associated with transfusing labile blood products can be infectious or noninfectious in nature. In Quebec, thanks to the preventive measures in place to counter infectious risks, the most common complications are of the noninfectious type. These include human errors that lead to the transfusion of the wrong product. (USE OF THE INTERCEPT BLOOD SYSTEM PROCESS WORLDWIDE) In March 2015, the Intercept process was being used in 22 countries to treat platelets, and 13 countries to treat plasma. For instance, Switzerland treats all platelet concentrates, and Belgium treats more than 90% of them with amotosalen and UVA. Other jurisdictions comparable to Quebec, such as the United Kingdom and Australia/New Zealand, have decided not to introduce photochemical pathogen inactivation processes. The rationale behind their decisions is based, among other things, on their inefficiency (cost-effectiveness) and on the weakness of the evidence regarding the superiority, in terms of efficacy, of these processes over those currently in place. (PATHOGEN INACTIVATION) The Intercept Blood System process has been shown effective against a broad range of viruses, bacteria and protozoa during laboratory testing. It has limited efficacy against certain nonenveloped viruses, such as parvovirus B19, the hepatitis A virus (HAV), the hepatitis E virus (HEV) and the poliovirus. Furthermore, the Intercept Blood System process has been shown to be of limited effectiveness or ineffective in inactivating the Gram-negative bacterium Pseudomonas aeruginosa and the sporulating form of the Gram-negative bacterium Bacillus cereus. And it is ineffective against prions. (PROPERTIES AND EFFICACY OF LABILE BLOOD PRODUCTS TREATED WITH THE INTERCEPT BLOOD SYSTEM PROCESS) Laboratory and clinical studies, most of which are linked to the Cerus Corporation, show that the Intercept Blood System process does not have a negative impact on the coagulation properties or therapeutic efficacy of plasma. In vitro analyses have shown that treating platelets results in a reduction in their number, pH and response to hypotonic shock. In clinical studies, this translates into a slight decrease in post-transfusion platelet count increment and in the transfusion interval. (INCIDENCE OF ADVERSE EVENTS) In three retrospective, postmarketing hemovigilance studies involving more than 58,000 transfusions of Intercept-treated plasma, no significant difference in adverse effects was observed between the groups that received amotosalen-treated plasma and those that received conventional plasma. The use of amotosalen-treated platelets appears to cause an increase in the number of refractory patients. However, this result is associated with the lower post-transfusion platelet count increment in patients receiving amotosalen/UVA-treated platelets. Most of the studies selected suggest that the Intercept Blood System process does not change the incidence of adverse events. (LONG-TERM TOXICITY) Residual amotosalen and free and covalently bound photoproducts are present in labile blood products that have been treated with the Intercept Blood System process. No study concerning the potential risks of patients long-term exposure to such blood products was found. Because of the absence of clinical data, long-term toxicological, oncological and teratogenic risks in humans cannot be ruled out. (CHANGES TO CURRENT PRACTICES) The Intercept process for platelets could replace gamma irradiation, CMV serology testing and bacterial detection. However, modifying these measures would require Health Canada approval. Also, leukocyte reduction, bacterial cultures and screening are the subject of standards that prescribe their use in the production of labile blood products. (EFFICIENCY) The cost-effectiveness ratios from the studies examined range from $269,045/QALY to $43,648,879/QALY. They are largely above the acceptability thresholds for a health technology set by many countries. (BUDGET IMPACT) Adding Intercept to the preventive measures currently used by Héma-Québec to treat platelets and plasma could generate additional recurrent costs ranging from $9.5 million to $12.3 million per year. In all, this represents estimated additional costs of $107 million for a 10-year time horizon. (CONTEXTUAL AND EXPERIENTIAL DATA) According to the experts consulted, the current scientific data do not permit the conclusion that the Intercept Blood System process is superior to the preventive methods currently used in Quebec. The data on the process’s efficiency, the weakness of the evidence regarding the long-term toxicological risks, and the inability to treat all labile blood products are concerns for all the stakeholders consulted. The citizen members and the representatives of patient associations clearly expressed their concerns about blood product safety. However, these concerns are not limited to infectious risks, but extend to the entire blood system. It is felt that priority should be given to investing in other measures that would make it possible to meet more frequent and more urgent needs in Quebec’s blood system. CONCLUSION: The Intercept Blood System pathogen inactivation process offers the theoretical advantage of reducing the potential risks associated with a pathogenic agent that evades the current detection tests and with blood products obtained during the latency period of an infection in an asymptomatic donor. However, certain pathogens, such as nonenveloped viruses and prions, withstand this treatment. Furthermore, certain issues remain, such as potentially harmful residual compounds, the absence of a process for treating red blood cells, which account for 75% of Quebec’s transfusion needs, and the cost-effectiveness ratios above the generally accepted thresholds.

Authors' recommendations: INESSS believes that the relevance of introducing the Intercept Blood System pathogen inactivation process is currently limited in Quebec, given the following:  The risk of post-transfusion infections is currently very low in Quebec because of the preventive measures in place.  In the absence of a pathogen inactivation system for red blood cells or whole blood, approximately 75% of labile blood products cannot be treated.  Since certain types of pathogens withstand photochemical inactivation, the process’s efficacy against an emerging pathogen cannot be guaranteed.  There are no clinical data to rule out long-term toxicity or oncogenicity from residual amotosalen, which is a specific concern in pediatrics.  Few safety measures currently in place could be removed, mainly because of the absence of a process for treating red blood cells or whole blood.  The cost-utility ratio (QALY) of the procedure is much higher than the generally recognized acceptability thresholds.

Authors' methods: The MEDLINE (PubMed), EMBASE and Evidence-Based Medicine Reviews (EBMR) databases and the database of the International Network of Agencies for Health Technology Assessment (INAHTA) were queried. Relevant studies were selected using predefined PICOT criteria. The grey literature was searched as well. Among other things, guidelines, hemovigilance reports and health technology assessment (HTA) reports from Quebec, Canadian and international sources were consulted. CASP tools were used to assess the quality of clinical studies. For systematic reviews with or without meta-analysis and for HTA reports, R-AMSTAR tools and the INAHTA checklist were used, respectively. As well, a budget impact analysis was performed over a 10-year time horizon using MSSS forecasts. An advisory committee and a follow-up committee were formed. The members were invited, at different stages, to critique the research questions and comment on the data that had been gathered. The citizen members of INESSS’s Conseil scientifique, clinical excellence committees and standing scientific committees, as well as representatives of patient associations, were consulted for their perceptions of the risks, the anticipated benefits and the costs associated with pathogen inactivation processes. For these reasons, INESSS makes the following recommendation: Currently, the Intercept Blood System process should not be introduced into the production of labile blood products in Quebec.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/pertinence-de-lintroduction-dun-procede-dinactivation-des-pathogenes-pour-les-produits-sanguins-labiles-au-quebec.html

Year Published: 2017

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/pertinence-de-lintroduction-dun-procede-dinactivation-des-pathogenes-pour-les-produits-sanguins-labiles-au-quebec.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: Gouvernement du Québec