Intention-to-treat and transparency of related practices in randomized, controlled trials of anti-infectives.

BACKGROUND: Intention-to-treat (ITT) analysis is commonly recommended for use, due to its benefits on external validity, in randomized, controlled trials (RCTs). No published reports describe how ITT analysis, as well as alternative approaches, are used in anti-infective RCTs. The purpose of this study is to describe the extent to which ITT analysis and alternative data approaches are used, the practices used to handle missing subject data, and whether non-inferiority trials present both ITT and per protocol (PP) analyses. Results of this analysis will help guide end users of infectious diseases primary drug literature. METHODS: A cross-sectional study of RCTs of anti-infectives published from January 1, 2013 through December 31, 2014 was conducted. A PubMed search identified relevant articles published in five specialty infectious diseases journals and four general medical journals. Each article was reviewed by two independent investigators with discrepancies resolved by consensus. Descriptive statistics were used to quantify results. RESULTS: One hundred four articles met study criteria. The most common medication classes represented in the RCTs were hepatitis C antivirals (26 %), antibacterials (25 %), and antiretrovirals (21 %). Thirty studies (29 %) were non-inferiority trials. Most studies (77 %) described use of ITT or modified ITT (mITT) in their methods. Of the ITT and mITT studies, most (73 %) did not describe practices used to handle missing data. Most (97 %) non-inferiority trials described use of ITT, mITT, or both; however, only 15 (50 %) also described use of PP. CONCLUSIONS: RCTs of anti-infectives commonly employ ITT and mITT. Most do not describe how missing data were addressed. Non-inferiority trials of anti-infectives do not consistently employ both ITT and PP populations.

Dexmedetomidine for Alcohol Withdrawal Syndrome.

OBJECTIVE: To review available evidence evaluating dexmedetomidine in alcohol withdrawal syndrome (AWS) while identifying gaps in evidence for its use in this setting. DATA SOURCES: A MEDLINE search (1966-August 2015) to identify English-language articles evaluating the efficacy and safety of dexmedetomidine in alcohol withdrawal. Key words included alcohol, withdrawal, delirium tremens, and dexmedetomidine. Additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: All English-language observational studies, retrospective reviews, and clinical trials were included. Case reports and case series describing the use of dexmedetomidine in 10 or fewer patients were excluded. DATA SYNTHESIS: One randomized, controlled trial, 1 prospective observational study, and 6 retrospective reviews were identified. The only randomized, controlled trial identified showed that the addition of dexmedetomidine decreases benzodiazepine requirements more than placebo in the first 24 hours after initiation compared with the 24 hours prior to initiation (-56.8 mg vs -8 mg; P = 0.037). Overall, dexmedetomidine appears to lower benzodiazepine requirements in patients with AWS and decreases the sympathomimetic response seen in these patients. There was no convincing evidence that dexmedetomidine improves clinical endpoints in patients with AWS, such as need for mechanical ventilation or intensive care unit or hospital length of stay. CONCLUSIONS: Dexmedetomidine reduces hypertension and tachycardia in AWS and also reduces benzodiazepine requirements; however, the impact of these findings on important clinical endpoints is yet to be determined. Dexmedetomidine may be useful as adjunctive therapy; however, it cannot be recommended as a single agent in the management of AWS.