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Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                      \u2013associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic\n                      <jats:italic>Lactobacillus rhamnosus<\/jats:italic>\n                      GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      The objective of E-PROSPECT is to determine the incremental cost-effectiveness of\n                      <jats:italic>L. rhamnosus<\/jats:italic>\n                      GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer\u2019s perspective over a time horizon from ICU admission to hospital discharge.\n                    <\/jats:p>\n                    <jats:p>We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology\/laboratory testing, operative\/non-operative procedures and per-day hospital \u2018hoteling\u2019 costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical\/surgical\/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Study approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT01782755\">NCT01782755<\/jats:ext-link>\n                      ; Pre-results.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-036047","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T02:40:09Z","timestamp":1593398409000},"page":"e036047","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (E-PROSPECT): study protocol"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct01782755","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01782755","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9939-7348","authenticated-orcid":false,"given":"Vincent Issac","family":"Lau","sequence":"first","affiliation":[{"name":"Department of Critical Care, University of Alberta Faculty of Medicine and Dentistry, Edmonton, Alberta, Canada"},{"name":"Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah J","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada"},{"name":"Division of Critical Care, McMaster University, Hamilton, Ontario, 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