Systematic assessment of the influence of quality of studies on mistletoe in cancer care on the results of a meta-analysis on overall survival.

PURPOSE: Mistletoe treatment in cancer patients is controversial, and a Cochrane review concluded that due to heterogeneity, performing a meta-analysis was not suitable. However, several systematic reviews included meta-analyses in favor of mistletoe. The aim of this work was to assess the influence of the methodological quality of controlled studies on the results of a meta-analysis regarding overall survival.

METHODS: Between April and August 2022, Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL and Web of Science were systematically searched. In addition, reference lists of previously published meta-analyses were checked for relevant publications. A random effects meta-analysis with clustering was performed. The risk of bias within the studies was assessed using ROB 2.0 and ROBINS-I.

RESULTS: The search identified 4685 hits, and 28 publications reporting on 28 298 patients were included in the quantitative analysis. Overall, the analysis led to a significant result in favor of mistletoe therapy (overall HR = 0.61 with 95% CI [0.53;0.7]). According to our subgroup analysis of randomized studies, studies of higher quality (lower risk of bias) did not lead to a significant result in favor of mistletoe therapy (HR = 0.78; CI = [0.30; 2.00]).

CONCLUSIONS: In the case of mistletoe therapy, the results of the meta-analysis strongly depended on the methodological quality of the included studies. Calculating meta-analyses that include low-quality studies may lead to severe misinterpretation of the data.