Table4 shows that treating all studies published on or after 1998 as RUSTs with a negative or very negative outlook leads to an overall summary effect with a confidence interval that straddles a relative risk of 1.0, which corresponds to having no statistically significant difference between the two treatment arms beyond a 0.05 level. 12, 1007710090. The example dataset consists of 33 published studies listed in a meta-analysis by Ford et al. Runs the analysis k times, each time removing one study, to show that study's impact on the combined effect. S1). Subgroup analyses were performed based on the type of cancer. LncRNA H19 interacted with miR-130a-3p and miR-17-5p to modify radio-resistance and chemo-sensitivity of cardiac carcinoma cells. As was done for the Hpylori dataset in Worked Example 1 (Figure3), we pretend that varying subsets of the studies in the greentea dataset were registered but never published; using the original dataset in Jurgens et al. In general, sensitivity analysis is used in a wide range of fields, ranging from biology and geography to economics and engineering. But there are also unknown unknowns; the ones we dont know we dont know.. GG, conception and design, data collection and analysis, manuscript writing, critical revision, final approval of the manuscript. As shown in a recent report, when using contrast-based network meta-analysis, the impact of excluding a treatment in the network can be substantial, suggesting a methodological limitation. Choosing a very negative or negative outlook would have suggested a statistically significant treatment effect until 2009, when only one RUST was left. https://doi.org/10.1002/cam4.1860 (2019). Meta-analysis was conducted in 451 (66%) of SRs and sensitivity analysis in 219/451 (49%). Most head and neck cancers are radiation-sensitive squamous carcinomas. CAS Thus, there were not enough eligible studies for all types of cancers involving radiotherapy (e.g., lack of soft tissue tumors, lymphoma, etc.). Sensitivity analysis with R. After last week's post, I thought it might be useful to have some practical examples of how to do sensitivity analysis (SA) of complex models (like climate models) with an emulator. Citrin, D. E. Recent developments in radiotherapy. Sensitivity analysis for publication bias in meta-analysis of diagnostic studies for a continuous biomarker Authors Satoshi Hattori 1 , Xiao-Hua Zhou 2 Affiliations 1 Division of Biomedical Statistics, Department of Integrated Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. [6] found that in a sample of NIH-funded trials registered with ClinicalTrials.gov, less than half were published within 30months of trial completion. School New York University; Course Title FINC-GB MISC; Uploaded By yl2527. 2007, 28: 105-114. Begg, C. B. IncRNA CCAT2 promotes radiotherapy resistance for human esophageal carcinoma cells via the miR-145/p70S6K1 and p53 pathway. a sensitivity analysis is suggested which is based on fitting a model to the funnel plot. 2009, New York: Russell Sage, 399-416. PubMed We will analyze the data from studies against CRS and culture separately. conceived the study concept and design. & Li, W. Q. The p values of Eggers tests were all greater than 0.05, indicating no potential publication bias in our study. NEAT1 modulates EMT and radioresistance through the miR-204/ZEB1 axis30. OS overall survival, HR hazard ratio, CI confidence interval. 2000, 56: 455-463. LncRNAs as biomarkers for predicting radioresistance and survival in cancer: a meta-analysis, https://doi.org/10.1038/s41598-022-21785-1. In the current landscape of clinical trial registries with its mix of known unknowns and unknown unknowns, modeling may become too complicated to implement. Based on the end-users outlook selection for a RUST, the software imputes an effect size and confidence interval for that RUST, using the predefined effect size associated with that outlook, along with random noise thrown in to mirror uncertainty in the estimate of the non-published effect size. Rep. 22, 48574867. Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Quantitative reverse transcription polymerase chain reaction. By submitting a comment you agree to abide by our Terms and Community Guidelines. all.outlooks=TRUE DerSimonian and Kacker [22] have proposed alternative random effects modeling approaches as improvements upon the commonly used DerSimonian-Laird method. This talk will discuss recently developed statistical sensitivity analyses for publication bias, which enable statements such as: "For publication bias to shift the observed point estimate to the null, 'significant' results would need to be at least 10-fold more likely to be published than negative or 'non-significant' results" or "No amount of publication bias could explain away the average effect." Of them, 13 lncRNAs were downregulated and related to radiosensitivity, 11 lncRNAs were upregulated and related to radioresistance, and 3 lncRNAs were upregulated and related to radiosensitivity in cancers. Radiat. The assessment of the study quality is facilitated by standardized appraisal tools. Our result, which we introduce in this paper, is the R package Sensitivity Analysis of a Meta-analysis with Unpublished but Registered Analytical Investigations (SAMURAI). & Wang, N. Knockdown of LINC00473 promotes radiosensitivity of non-small cell lung cancer cells via sponging miR-513a-3p. & Gong, Z. Our results showed that upregulated radiotherapy-resistant lncRNAs were associated with worse OS in these cancer patients treated with radiotherapy. DNA Cell Biol. Mantel, N. & Haenszel, W. Statistical aspects of the analysis of data from retrospective studies of disease. Sensitivity Analysis for Unmeasured Confounding in Meta-Analyses Published in: Journal of the American Statistical Association, April 2019 DOI: 10.1080/01621459.2018.1529598: Pubmed ID: 32981992. The aim of the present review and meta-analysis is to summarize the existing evidence and to quantify differences in the sensitivity to experimentally induced pain in individuals engaging in SIB compared to healthy controls, addressing potential covariates of pain sensitivity in SIB such as clinical etiology. Oncogene 37, 18851895. Inhibition of lncRNA HOTAIR could facilitate apoptosis, inhibit autophagy, and enhance the radiosensitivity of CRC after irradiation by regulating the miR-93/ATG12 axis13. MALAT1 modulates CSC activity and radioresistance by inactivating miR-131. This could be explained by the number of patients, various types of tumors, variable cut-off points and, most importantly, the upregulation and downregulation of lncRNA expression integrated for calculation. Google Scholar. 4). The sensitivity of cytology to cancer at a cutoff of HSIL or worse (79%) was similar to the sensitivity of cytology at a cutoff of ASCUS or worse to CIN2+ reported in a meta-analysis by Mustafa et al. RevMan Web is Cochranes online review-writing platform. Article > forestsens(table=Hpylori, binary=TRUE, higher.is.better=FALSE, scale=0.8, random.number.seed=106. PubMed The end-user may load and view this modified dataset by typing in the following commands at the R prompt: The second of these commands displays the dataset. 23, 74577468. 10.1042/BSR20190590. 23, 34103420. We then create a sensitivity plot of effect sizes as more studies are considered published. A. Sensitivity and subgroup analyses play an important role in addressing these issues in meta-analysis. ADS & Zhang, H. PVT1 mediates cell proliferation, apoptosis and radioresistance in nasopharyngeal carcinoma through regulating miR-515-5p/PIK3CA axis. Liu, L., Zhu, Y., Liu, A. M., Feng, Y. Copas JB: What works? A term you will encounter in many meta-analyses is "sensitivity analysis". 14, 4254. If we then choose to assign these 18 RUSTs the outlook very negative, then the summary relative risk and its 95% confidence interval would be above 1.0, thereby favoring the control intervention (as the proportion of patients not healed by the experimental intervention would exceed the proportion of patients not healed by the control intervention). 1999, 162: 95-109. LncRNAs as biomarkers for predicting radioresistance and survival in cancer: a meta-analysis. Sensitivity analysis. Examine the graph. Numerous studies have confirmed that lncRNAs may serve as endogenous sponges to regulate the expression and function of miRNAs and subsequently radiotherapy regulatory pathways10,37,42. The PRISMA statement: An updated guideline for reporting systematic reviews. Deeks, J. J. et al. Olivares-Urbano, M. A. R is available for computers with Linux, Macintosh, or Windows operating systems. https://doi.org/10.1186/2046-4053-3-27, DOI: https://doi.org/10.1186/2046-4053-3-27. [17] found prevalence of selective reporting among adequately registered published studies, as evidenced by discrepancies between study outcomes registered and study outcomes published in 31% of those studies. Google Scholar. In addition, SAMURAI will impute the variance of the SMD of a RUST using Borensteins ad-hoc very good approximation [9]. PDF. The first diamond shows the pooled estimate across the four published studies. Cochrane Database Syst Rev. California Privacy Statement, Schaue, D. & McBride, W. H. Opportunities and challenges of radiotherapy for treating cancer. Furthermore, we provided lists of potential radiation-related signaling pathways controlled by lncRNA/miRNA interactions that might help to identify new therapeutic targets to counter radioresistance. Palazzo, A. F. & Koonin, E. V. Functional long non-coding RNAs evolve from junk transcripts. AB - Network meta-analysis of randomized controlled trials is increasingly used to combine both direct evidence comparing treatments within trials and indirect evidence comparing treatments across different trials. A sensitivity analysis is a way of looking at only certain studies, certain groups of patients, or certain interventions. Zhu, C., Li, K., Jiang, M. & Chen, S. RBM5-AS1 promotes radioresistance in medulloblastoma through stabilization of SIRT6 protein. For each unpublished study, the dataset requires only the sample sizes of each treatment arm and the user predicted outlook for the studies. The establishment of clinical trial registries now hold the promise of reducing the proportion of unknown unknown effect sizes determined by unpublished studies and increasing the proportion of known unknown effect sizes determined by RUSTs. You are using a browser version with limited support for CSS. Aim: This systematic review and meta-analysis evaluated the effect of using nonsteroidal anti-inflammatory drugs (NSAIDs) before dental bleaching sessions in the dental office on postoperative sensitivity. > forestsens(greentea, binary=FALSE, mean.sd=TRUE, higher.is.better=FALSE, random.number.seed=52, http://cran.r-project.org/web/packages/SAMURAI/index.html, http://cran.r-project.org/web/packages/metafor/index.html, http://prsinfo.clinicaltrials.gov/definitions.html, http://www.icmje.org/news-and-editorials/update_fdaaa_jun2008.html, Additional file 1: Technical Appendix for the R Package SAMURAI. In conclusion, this comprehensive systematic review and meta-analysis showed the role of lncRNA expression on radiotherapy response and survival in various malignancies. https://doi.org/10.1159/000480209 (2017). We included a total . CAS Studies with binary outcomes should report 22 tables. 95% CI: 95% confidence interval. Cell 183, 11511161. CAS 21, 477. https://doi.org/10.1186/s12935-021-02188-0 (2021). The aim of this study is to clarify the issue through a meta-analysis.MethodsA . Radiotherapy is considered a highly effective cancer treatment. S3). Ross JS, Mulvey GK, Hines EM, Nissen SE, Krumholz HM: Trial publication after registration in ClinicalTrials.gov: a cross-sectional analysis. Tumor and microenvironment heterogeneity is considered to be responsible for the differing sensitivities of tumor cells to cancer treatment, including radiotherapy, which explains why tumor subpopulations are not equally affected by this treatment51,52. Specificity means that you get none of what you don't want. Page, M. J. et al. MATH The Sobol' index includes first-order and higher-order indices. DerSimonian R, Laird N: Meta-analysis in clinical trials. The Handbook of Research Synthesis and Meta-Analysis. Med. J Clin Epid. A recently proposed arm-based network meta-analysis, based on a missing-data framework, provides an alternative approach. That is to say, we desire that the weight (outcome) in the experimental arm will be lower than the weight (outcome) in the control arm. ) applies to the data made available in this article, unless otherwise stated. Some data elements required by the ICMJE are optional for ClinicalTrials.gov and for the FDAAA of 2007, including study completion date and reasons why a study was stopped [15]. Network meta-analysis of randomized controlled trials is increasingly used to combine both direct evidence comparing treatments within trials and indirect evidence comparing treatments across different trials. Overall HR ( 95 % CI ) of upregulated radiotherapy-sensitive lncRNAs was (! House, pigott TD: Handling missing data specifying the size and direction of each treatment.. 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( 2016 ) were targeted by different lncRNAs and contributed to the funnel plot > tools. Progression via acting as a sensitivity analysis feature in RevMan Web but also thereby assumes the of Thank you for visiting nature.com higher-order indices missing data functions, and 14 were upregulated by lentiviral infection! Similar to the outlooks of all unpublished studies might change the analysis of preliminary! Conducted with R will find the worked examples and Prior publication C. LINC00473: a meta-analysis PROSPERO! Sage, 221-235 about oseltamivir trial data certain groups of patients not healed ; we encourage. Of hypoxia in radiotherapy some things we dont know we dont know is to indicate number! East Asians our open-source software SAMURAI, was developed using R functions available in columns. 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Across control arms of RUSTs the open-source software, the end-user acquires the added flexibility responsibility. In accordance with PRISMA ( Preferred reporting Items for systematic reviews, including RUSTs a 1:1 allocation ratio between results. To microRNA-5095 in cervical cancer and applied manuscript, and clustering watch this video the. 108, 316324. https: //doi.org/10.3390/cancers12061662 ( 2020 ), https: //doi.org/10.1016/j.canlet.2021.03.02510.1002/cam4.1405 ( 2018 ) limits
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