The umbrella trial has received increasing attention in the design of clinical trials for oncology drugs in recent years. This trial design categorizes a single disease into multiple sub-types based on predictive biomarkers or other predictive factors, and simultaneously evaluates the efficacy of multiple targeted therapies. When compared with the traditional drug development model of phase Ⅰ, phaseⅡ, and phase Ⅲ randomized controlled trials, umbrella trials are a more scientifically rigorous trial design that can speed up drug evaluation to address the conflict between numerous untested drugs and diseases with a lack of effective treatment options. This article will focus on the concept, main characteristics, eligibility criteria, design and statistical considerations, ethical considerations, and future directions of umbrella trials, with the aim of providing methodological guidance for the design of clinical trials for oncology drugs.
Objective To systematically review the efficacy of long-acting antibacterial material in the prevention of secondary urinary infection. Methods PubMed, The Cochrane Library, CNKI, CBM, WanFang Data and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy of long-acting antibacterial material in the prevention of secondary urinary infection from inception to November, 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software. Results A total of 16 RCTs were included. The results of meta-analysis showed that: the long-acting antibacterial material group was superior to the general intervention group in morbidity of secondary urinary infection (Peto OR=0.17, 95%CI 0.13 to 0.23, P<0.000 01), and bacterial positive rate of secondary urinary infection (Peto OR=0.15, 95%CI 0.08 to 0.27,P<0.000 01). Conclusion Current evidence shows that long-acting antibacterial material can effectively reduce the infection rates of secondary urinary infection. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
ObjectiveZero-events studies frequently occur in systematic reviews of adverse events, which consist of an important source of evidence. We aimed to examine how evidence of zero-events studies was utilized in the meta-analyses of systematic reviews of adverse events.MethodsWe conducted a survey of systematic reviews published in two periods: January 1, 2015 to January 1, 2020 and January 1, 2008, to April 25, 2011. Databases were searched for systematic reviews that conducted at least one meta-analysis of any healthcare intervention and used adverse events as the exclusive outcome. An adverse event was defined as any untoward medical occurrence in a patient or subject in healthcare practice. We summarized the frequency of occurrence of zero-events studies in eligible systematic reviews and how these studies were dealt with in the meta-analyses of these systematic reviews.ResultsWe included 640 eligible systematic reviews. There were 406 (63.45%) systematic reviews involving zero-events studies in their meta-analyses, among which 389 (95.11%) involved single-arm-zero-events studies and 223 (54.93%) involved double-arm-zero-events studies. The majority (98.71%) of these systematic reviews incorporated single-arm-zero-events studies into the meta-analyses. On the other hand, the majority (76.23%) of them excluded double-arm-zero-events studies from the meta-analyses, of which the majority (87.06%) did not discuss the potential impact of excluding such studies. Systematic reviews published at present (2015-2020) tended to incorporate zero-events studies in meta-analyses than those published in the past (2008-2011), but the difference was not significant [proportion difference=–0.09, 95%CI (–0.21, 0.03), P=0.12].ConclusionSystematic review authors routinely treated studies with zero-events in both arms as "non-informative" carriers and excluded them from their reviews. Whether studies with no events are "informative" or not, largely depends on the methods and assumptions applied, thus sensitivity analyses using different methods should be considered in future meta-analyses.