{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T09:35:31Z","timestamp":1773221731296,"version":"3.50.1"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T00:00:00Z","timestamp":1600992000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014131","name":"McGill University Health Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014131","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fonds de Recherche Sant\u00e9 Qu\u00e9bec"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The effect of participation in a clinical trial on concomitant off-study investigational drug use has not been described. We sought to determine if participation in the Daptomycin as Adjunctive Therapy for Staphylococcus aureus bacteremia (DASH) trial increased overall daptomycin prescribing at study sites.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We retrospectively analyzed daptomycin use for 8 years preceding the trial, off-study daptomycin use during the trial itself (31 months), and daptomycin use for 6 fiscal months after trial completion. We used a segmented linear regression analysis of an interrupted time series to analyze changes in each drug\u2019s defined daily doses (DDD) per 1000 patient-days. As a control, we analyzed use of linezolid over these periods and also accounted for rates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) infections.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>For 1.5 years before the DASH trial, daptomycin use was decreasing by \u20130.30 DDD per 1000 patient-days per fiscal period (95% CI, \u20130.52 to \u20130.07). Following the initiation of the study, there was a statistically significant increase in daptomycin use of 0.28 DDD per 1000 patient-days per fiscal period (95% CI, 0.03 to 0.52), despite low, stable rates of MRSA and VRE infections. Following trial completion, daptomycin use decreased back toward prestudy rates. Use of linezolid remained stable throughout.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Despite the DASH trial being a negative study, it impacted the prescribing habits of local clinicians during recruitment. Trialists should be aware of potential off-target study effects, and prescribers should be wary of early uptake of interventions before definitive study results.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofaa449","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T21:24:48Z","timestamp":1600982688000},"source":"Crossref","is-referenced-by-count":4,"title":["Clinical Trials Increase Off-Study Drug Use: A Segmented Time-Series Analysis"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-0396","authenticated-orcid":false,"given":"Guillaume","family":"Butler-Laporte","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Division of Medical Microbiology, Department of Pathology and Laboratory Medicine, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4867-2063","authenticated-orcid":false,"given":"Matthew P","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Division of Medical Microbiology, Department of Pathology and Laboratory Medicine, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J G","family":"Thirion","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Department of Pharmacy, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"De L\u2019\u00c9toile-Morel","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Division of Medical Microbiology, Department of Pathology and Laboratory Medicine, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Frenette","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Division of Medical Microbiology, Department of Pathology and Laboratory Medicine, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katryn","family":"Paquette","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7948-3161","authenticated-orcid":false,"given":"Alexander","family":"Lawandi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Division of Medical Microbiology, Department of Pathology and Laboratory Medicine, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily G","family":"McDonald","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, Department of Medicine, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Clinical Practice Assessment Unit, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, 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