ABSTRACT
Risk of bias (RoB) assessment is essential to the systematic review methodology. The new version of the Cochrane RoB tool for randomized trials (RoB 2) was published in 2019 to address limitations identified since the first version of the tool was published in 2008 and to increase the reliability of assessments. This study analyzed the frequency of usage of the RoB 2 and the adequacy of reporting the RoB 2 assessments in non-Cochrane reviews published in 2020. This meta-research study included non-Cochrane systematic reviews of interventions published in 2020. For the reviews that used the RoB 2 tool, we analyzed the reporting of the RoB 2 assessment. Among 3880 included reviews, the Cochrane RoB 1 tool was the most frequently used (N = 2228; 57.4%), followed by the Cochrane RoB 2 tool (N = 267; 6.9%). From 267 reviews that reported using the RoB 2 tool, 213 (79.8%) actually used it. In 26 (12.2%) reviews, erroneous statements were used to indicate the RoB 2 assessment. Only 20 (9.4%) reviews presented a complete RoB 2 assessment with a detailed table of answers to all signaling questions. The judgment of risk of bias by the RoB 2 tool was not justified by a comment in 158 (74.2%) reviews. Only in 33 (14.5%) of reviews the judgment in all domains was justified in the accompanying comment. In most reviews (81.7%), the RoB was inadequately assessed at the study level. In conclusion, the majority of non-Cochrane reviews published in 2020 still used the Cochrane RoB 1 tool. Many reviews used the RoB 2 tool inadequately. Further studies about the uptake and the use of the RoB 2 tool are needed.
Subject(s)
Bias , Randomized Controlled Trials as Topic , Research Design , Systematic Reviews as Topic , Humans , Reproducibility of Results , Risk Assessment , PublicationsABSTRACT
Obinutuzumab (G) has become part of front-line treatment of follicular lymphoma (FL) based on results of a large randomized study. Data on patients treated outside of clinical trials are lacking. We have retrospectively investigated efficacy and safety of G-based immunochemotherapy regimens in 114 patients treated in a real-life setting during a period of 2 years, largely coinciding with the COVID-19 pandemic. The response rate was 93.8%; 18-months overall (OS) and progression-free survival (PFS) were 88% and 84%, respectively. Patients treated with G-cyclophosphamide, vincristine and glucocorticoid + doxorubicine (CHOP) had statistically significantly superior OS and PFS compared to patients treated with G-bendamustine (G-B) (P = 0.002 and P = 0.006, respectively) due to an increase in lethal infections, most notably COVID-19, in the latter group. A total of 12 patients died during follow-up; 9 of 61 treated with G-B, 1 of 49 treated with G-CHOP and 2 of 4 treated with G-cyclophosphamide, vincristine and glucocorticoid (CVP). SARS-CoV-2 infection was diagnosed in 20 (17.5%) patients. All of the 7 treated with G-CHOP recovered, while 4 of 12 treated with G-B died. Immunoglobulin levels and severity of neutropenia were similar between the groups. In multivariate analysis, G-B in comparison to G-CHOP was an independent prognostic factor (P = 0.044, hazard ratio = 9.81) after adjustment for age, sex and Follicular Lymphoma International Prognostic Index (FLIPI). Based on our experience G has excellent antilymphoma activity in patients receiving front-line treatment for FL in real-life setting, but during the COVID-19 pandemic, it should be preferentially combined with CHOP, at least in patients younger than 65.
ABSTRACT
BACKGROUND: Clinical decisions are made based on Cochrane reviews, but the implementation of results of evidence syntheses such as Cochrane reviews is problematic if the evidence is not prepared consistently. All systematic reviews should assess the risk of bias (RoB) in included studies, and in Cochrane reviews, this is done by using Cochrane RoB tool. However, the tool is not necessarily applied according to the instructions. In this study, we aimed to determine the types of bias and their corresponding judgements noted in the 'other bias' domain of Cochrane RoB tool. METHODS: We analyzed Cochrane reviews that included randomized controlled trials (RCTs) and extracted data regarding 'other bias' from the RoB table and accompanying support for the judgment. We categorized different types of other bias. RESULTS: We analyzed 768 Cochrane reviews that included 11,369 RCTs. There were 602 (78%) Cochrane reviews that had 'other bias' domain in the RoB tool, and they included a total of 7811 RCTs. In the RoB table of 337 Cochrane reviews for at least one of the included trials it was indicated that no other bias was found and supporting explanations were inconsistently judged as low, unclear or high RoB. In the 524 Cochrane reviews that described various sources of other bias, there were 5762 individual types of explanations which we categorized into 31 groups. The judgments of the same supporting explanations were highly inconsistent. We found numerous other inconsistencies in reporting of sources of other bias in Cochrane reviews. CONCLUSION: Cochrane authors mention a wide range of sources of other bias in the RoB tool and they inconsistently judge the same supporting explanations. Inconsistency in appraising risk of other bias hinders reliability and comparability of Cochrane systematic reviews. Discrepant and erroneous judgments of bias in evidence synthesis may hinder implementation of evidence in routine clinical practice and reduce confidence in otherwise trustworthy sources of information. These results can help authors of Cochrane and non-Cochrane reviews to gain insight into various sources of other bias that can be found in trials, and also to help them avoid mistakes that were recognized in published Cochrane reviews.
