Dose-response meta-analysis, as a subset of meta-analysis, plays an important role in dealing with the relationship between exposure level and risk of diseases. Traditional models limited in linear regression between the independent variables and the dependent variable. With the development of methodology and functional model, Nonlinear regression method was applied to dose-response meta-analysis, such as restricted cubic spline regression, quadratic B-spline regression. However, in these methods, the term and order of the independent variables have been assigned that may not suit for any trend distribution and it may lead to over fitting. Flexible fraction polynomial regression is a good method to solve this problem, which modelling a flexible fraction polynomial and choosing the best fitting model by using the likelihood-ratio test for a more accurate evaluation. In this article, we will discuss how to conduct a dose-response meta-analysis by flexible fraction polynomial.
Objective To systematically review the dose-response relationship between cadmium exposure and the risk of stroke onset. Methods The PubMed, Web of Science, Cochrane Library, Embase, CNKI, VIP, WanFang Data, and CBM databases were electronically searched to collect studies related to objectives from inception to June 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed using Stata 15.1 software. Results There were 10 studies that involved 28 250 participants, and 7 of them were prospective cohort studies and 3 were case-control studies. Meta-analysis results showed that cadmium exposure significantly increased the risk of stroke (RR=1.39, 95%CI 1.20 to 1.59, P<0.01), blood cadmium exposure significantly increased the risk of stroke (RR=1.79, 95%CI 1.34 to 2.25, P<0.01), urinary cadmium exposure significantly increased the risk of stroke (RR=1.30, 95%CI 1.09 to 1.52, P<0.01). Blood cadmium exposure had a significantly nonlinear dose-response relationship associated with an increased risk of stroke (χ2=8.56, P<0.05). The risk of stroke increased by 15% with the blood cadmium exposure concentration of 0.8 μg/L (RR=1.15, 95%CI 0.98 to 1.36), and 51% with the blood cadmium exposure concentration of 1.2 μg/L (RR=1.51, 95%CI 1.14 to 2.01) than those without blood cadmium exposure. Urinary cadmium exposure had significantly linear dose-response relationship associated with an increased risk of stroke (χ2=2.47, P=0.12). The risk of stroke increased by 26% with the urinary cadmium exposure concentration of 0.8 μg/g (RR=1.26, 95%CI 1.20 to 1.31), and 31% with the urinary cadmium exposure concentration of 1.2 μg/g (RR=1.31, 95%CI 1.27 to 1.36) than those without urinary cadmium exposure. Conclusion Cadmium exposure increases the risk of stroke. There was a significant dose-response relationship between cadmium exposure and the risk of stroke.
Dose-response meta-analysis, an important tool in investigating the relationship between a certain exposure and risk of disease, has been increasingly applied. Traditionally, the dose-response meta-analysis was only modelled as linearity. However, since the proposal of more powerful function models, which contains both linear, quadratic, cubic or more higher order term within the regression model, the non-linearity model of dose-response relationship is also available. The packages suit for R are available now. In this article, we introduced how to conduct a dose-response meta-analysis using dosresmeta and mvmeta packages in R.
Dose-response meta-analysis serves an important role in investigating the dose-response relationship between independent variables (e.g. dosage) and disease outcomes. Traditional dose-response meta-analysis model is based on one independent variable to consider its own dose-specific effect on the outcome. However, for drug clinical trials, it generally involves two-dimensions of the treatment, such as dosage and course of treatment. These two-dimensions tend to be associated with each other. When neglecting their correlations, the results may be at risk of bias. Moreover, taking account of the "combined effect” of dosage and time on outcome has more clinical value. Therefore, in this article, based on traditional dose-response meta-analysis model, we propose a three-dimension model for dose-response meta-analysis which considers both the effect of dosage and time, to provide a solution for the above-mentioned problems in a traditional model.
When investing the relationship between independent and dependent variables in dose-response meta-analysis, the common method is to fit a regression function. A well-established model should take both linear and non-linear relationship into consideration. Traditional linear dose-response meta-analysis model showed poor applicability since it was based on simple linear function. We introduced a piecewise linear function into dose-response meta-analysis model which overcame this problem. In this paper, we will give a detailed discussion on traditional linear and piecewise linear regression model in dose-response meta-analysis.
As a valid method in systematic review, dose-response meta-analysis is widely used in investigating the relationship between independent variable and dependent variable, and which usually based on observational studies. With large sample size, observational studies can provide a reasonable amount of statistical power for meta-analysis. However, due to the design defects of observational studies, they tend to introduce many kinds of biases, which may influence the final results that make them deviation from the truth. Given the dead zone of methodology, there is no any bias adjusting method in dose-response meta-analysis. In this article, we will introduce some bias adjusting methods from other observational-study-based meta-analysis and make them suit for dose-response meta-analysis, and then compare the advantages and disadvantages of these methods.
Dose-response meta-analysis is being increasingly applied in evidence production and clinical decision. The research method, synthesizing certain dose-specific effects across studies with the same target question by a certain types of weighting schedule to get a mean dose-response effect, is to reflect the dose-response relationship between certain exposure and outcome. Currently, the most popular method for dose-response meta-analysis is based on the classical "two-stage approach", with the advantage that it allows fixed- or random-effect model, according to the amount of heterogeneity in the model. There are two types of random-effect model available for dose-response meta-analysis, that is, the generally model and the coefficient-correlation-adjusted model. In this article, we briefly introduce two models and illustrate how they are applied in Stata software, which is expected to provide theoretical foundation for evidence-based practice.
ObjectiveTo systematically review the dose-response relationship between body mass index (BMI) and all-cause mortality in the elderly with frailty.MethodsPubMed, EMbase, Web of Science, CNKI, VIP, WanFang Data, and CBM databases were electronically searched to collect cohort studies on the association of BMI and mortality in frail adults from inception to November 2019. Two reviewers independently screened literature, extracted data and assessed risk bias of included studies; Stata 15.0 software was then used to analyze the dose-response analysis of BMI and mortality by restricted cubic spline function and generalized least squares method.ResultsA total of 4 cohort studies involving 12 861 frail adults were included. Meta-analysis results showed that compared with normal BMI, the frail elderly who were overweight (HR=0.80, 95%CI 0.74 to 0.88, P<0.001) and obese (HR=0.89, 95%CI 0.79 to 1.00, P=0.047) had lower all-cause mortality. The results of dose-response meta-analysis showed that there was a non-linear relationship between BMI and all-cause mortality in the elderly with frailty (P value for nonlinearity was 0.035), for which the elderly with frailty had a BMI nadir of 27.5-31.9 kg/m2. For linear trends, and when BMI was less than 27.5 kg/m2, the risk of all-cause death was reduced by 4% for every 1 kg/m2 increase in BMI (RR=0.96, 95%CI 0.90 to 1.03, P=0.320), when BMI was greater than 27.5 kg/m2, the risk of all-cause death increased by 4% for every 1 kg/m2 increase in BMI (RR=1.04, 95%CI 1.03 to 1.05, P<0.001).ConclusionsThere is a paradox of obesity and a significant nonlinear relationship between BMI and all-cause mortality in the frailty elderly, with the lowest all-cause mortality in the frailty elderly at BMI 27.5-31.9 kg/m2. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusions.
According to the heterogeneity between dose-response data across different studies and the potential nonlinear trend within the dose-response relationship, there are several models for trend estimation from summarized dose-response data, with applications to meta-analysis. However, up to now, there is no guideline of conducting a metaanalysis of dose-response data. After summarizing the previous papers, this paper focuses on how to select the right model for conducting a meta-analysis of dose-response data based on the heterogeneity across different studies, the goodness of fit, and the P value of overall association between exposure and event. Then a preliminary statistical process of conducting a meta-analysis of dose-response data is proposed.
Dose-response relationship model has been widely used in epidemiology studies, as well as in evidence-based medicine area. In dose-response meta-analysis, the results are highly depended on the raw data. However, many primary studies did not provide sufficient data and led the difficulties in data analysis. The efficiency and response rate of collecting the raw data from original authors were always low, thus, evaluating and transforming the missing data is very important. In this paper, we summarized several types of missing data, and introduced how to estimate the missing data and transform the effect measure using the existed information.