Consequently, there is a small risk that we may have missed very recent publications in languages other than German or English. German. In addition, we searched ClinicalTrials.gov to identify unpublished studies. We dually reviewed the abstracts and ortho-iodoHoechst 33258 full-text articles based on a priori defined ortho-iodoHoechst 33258 inclusion criteria, rated the risk of bias of included studies, and assessed the strength of the evidence for each outcome of interest. Because data was insufficient for quantitative synthesis, we summarized results narratively. Results We identified three RCTs (randomized controlled trials) meeting our eligibility criteria, which included data on 1003 patients. We found moderate evidence for comparable event rates (20.05% vs. 18%, HR (hazard ratio) 0.88, CI 95% = 0.62C1.27), and mortality rates (10% vs. 8%, HR 0.76, CI 95% = 0.44C1.32) after 1.7 years for patients receiving trastuzumab IV and for patients receiving SC. Results remained comparable after 3.3 years, though evidence lacked strength due to a high dropout rate. All trials reported more adverse events among the SC group than in the IV group. Evidence for these findings was of moderate strength. Nevertheless, more than 85% of the patients favored trastuzumab SC over IV. Results concerning serious adverse events appeared to be heterogeneous. Conclusion Results of studies indicate similar efficacy between the two routes of administration. The higher rates of adverse events for SC administration were mainly attributable to injection siteCrelated events. The clinical decision of whether to administer trastuzumab SC or IV requires the concern of several factors and should be determined individually. as search concepts. When possible, we used both subject headings (MeSH) and free text in our searches. We ran a similar article search for the first 100 linked articles in PubMed using publications [24C26] identified through preliminary searching (see Additional file 1 for complete search strategies). We limited searches to studies on humans published in German and English from inception to the search date. An experienced information specialist conducted these searches. In addition, we searched the register ClinicalTrials.gov and reference lists of included studies and reviews. Eligibility criteria We included studies addressing our predefined inclusion criteria outlined in Table ?Table11. Table 1 Eligibility criteria of included studies PopulationWomen with HER2-positive breast cancerInterventionNeoadjuvant or adjuvant treatment with subcutaneous trastuzumabControlNeoadjuvant or adjuvant treatment with intravenous trastuzumabOutcomes? Efficacy (overall survival, event-free survival) ? Safety: overall risk of adverse events, serious adverse events, discontinuation because of adverse events ? Patients preferences Study designRCTs, systematic reviews, and meta-analyses Open in a separate window human epidermal growth factor receptor, randomized controlled trial Rcan1 Study selection Two reviewers (A.G. and M.V.) independently screened abstracts and full-text articles using Covidence systematic review software [27]. We developed and pilot-tested abstract and full-text review forms based on the inclusion and exclusion criteria presented above. We retrieved full-text articles of all potentially relevant citations. Reviewers resolved conflicts in decisions regarding inclusion or exclusion by consensus. Data abstraction We abstracted information on population characteristics, interventions, route of administration, and outcomes of interest. One reviewer (M.V.) conducted data abstraction, a second reviewer (A.G.) checked data for completeness and correctness. Risk of bias assessment Both reviewers mentioned above ortho-iodoHoechst 33258 independently assessed the risk of bias ortho-iodoHoechst 33258 of randomized controlled trials using the Cochrane risk of bias tool [28]. They assessed the risk of bias for each outcome of interest and resolved differences by consensus. Grading the strength of evidence We graded the strength of evidence based on the guidance established for the Evidence-based Practice Center Program of the Agency for Healthcare ortho-iodoHoechst 33258 Research and Quality [29]. This approach incorporates four key domains: risk of bias, consistency, directness, and precision of the evidence. It also considers other domains that may be.