Interventions to reduce the risk of surgically transmitted Creutzfeldt-Jakob disease: a cost-effective modelling review.

BACKGROUND Creutzfeldt-Jakob disease is a fatal neurological disease caused by abnormal infectious proteins called prions. Prions that are present on surgical instruments cannot be completely deactivated; therefore, patients who are subsequently operated on using these instruments may become infected. This can result in surgically transmitted Creutzfeldt-Jakob disease. OBJECTIVE To update literature reviews, consultation with experts and economic modelling published in 2006, and to provide the cost-effectiveness of strategies to reduce the risk of surgically transmitted Creutzfeldt-Jakob disease. METHODS Eight systematic reviews were undertaken for clinical parameters. One review of cost-effectiveness was undertaken. Electronic databases including MEDLINE and EMBASE were searched from 2005 to 2017. Expert elicitation sessions were undertaken. An advisory committee, convened by the National Institute for Health and Care Excellence to produce guidance, provided an additional source of information. A mathematical model was updated focusing on brain and posterior eye surgery and neuroendoscopy. The model simulated both patients and instrument sets. Assuming that there were potentially 15 cases of surgically transmitted Creutzfeldt-Jakob disease between 2005 and 2018, approximate Bayesian computation was used to obtain samples from the posterior distribution of the model parameters to generate results. Heuristics were used to improve computational efficiency. The modelling conformed to the National Institute for Health and Care Excellence reference case. The strategies evaluated included neither keeping instruments moist nor prohibiting set migration; ensuring that instruments were kept moist; prohibiting instrument migration between sets; and employing single-use instruments. Threshold analyses were undertaken to establish prices at which single-use sets or completely effective decontamination solutions would be cost-effective. RESULTS A total of 169 papers were identified for the clinical review. The evidence from published literature was not deemed sufficiently strong to take precedence over the distributions obtained from expert elicitation. Forty-eight papers were identified in the review of cost-effectiveness. The previous modelling structure was revised to add the possibility of misclassifying surgically transmitted Creutzfeldt-Jakob disease as another neurodegenerative disease, and assuming that all patients were susceptible to infection. Keeping instruments moist was estimated to reduce the risk of surgically transmitted Creutzfeldt-Jakob disease cases and associated costs. Based on probabilistic sensitivity analyses, keeping instruments moist was estimated to on average result in 2.36 (range 0-47) surgically transmitted Creutzfeldt-Jakob disease cases (across England) caused by infection occurring between 2019 and 2023. Prohibiting set migration or employing single-use instruments reduced the estimated risk of surgically transmitted Creutzfeldt-Jakob disease cases further, but at considerable cost. The estimated costs per quality-adjusted life-year gained of these strategies in addition to keeping instruments moist were in excess of £1M. It was estimated that single-use instrument sets (currently £350-500) or completely effective cleaning solutions would need to cost approximately £12 per patient to be cost-effective using a £30,000 per quality-adjusted life-year gained value. LIMITATIONS As no direct published evidence to implicate surgery as a cause of Creutzfeldt-Jakob disease has been found since 2005, the estimations of potential cases from elicitation are still speculative. A particular source of uncertainty was in the number of potential surgically transmitted Creutzfeldt-Jakob disease cases that may have occurred between 2005 and 2018. CONCLUSIONS Keeping instruments moist is estimated to reduce the risk of surgically transmitted Creutzfeldt-Jakob disease cases and associated costs. Further surgical management strategies can reduce the risks of surgically transmitted Creutzfeldt-Jakob disease but have considerable associated costs. STUDY REGISTRATION This study is registered as PROSPERO CRD42017071807. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 11. See the NIHR Journals Library website for further project information.

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