Subscribe to the gold package and get unlimited access to Shamra Academy
Register a new userImplementation of an alternative method for assessing competing risks: restricted mean time lost
72
0
0.0
(
0
)
Added by
Zheng Chen
Publication date
2021
fields
Mathematical Statistics
and research's language is
English
Ask ChatGPT about the research
No Arabic abstract
In clinical and epidemiological studies, hazard ratios are often applied to compare treatment effects between two groups for survival data. For competing risks data, the corresponding quantities of interest are cause-specific hazard ratios (CHRs) and subdistribution hazard ratios (SHRs). However, they all have some limitations related to model assumptions and clinical interpretation. Therefore, we introduce restricted mean time lost (RMTL) as an alternative that is easy to interpret in a competing risks framework. We propose a hypothetical test and sample size estimator based on the difference in RMTL (RMTLd). The simulation results show that the RMTLd test has robust statistical performance (both type I error and power). Meanwhile, the RMTLd-based sample size can approximately achieve the predefined power level. The results of two example analyses also verify the performance of the RMTLd test. From the perspectives of clinical interpretation, application conditions and statistical performance, we recommend that the RMTLd be reported with the HR when analyzing competing risks data and that the RMTLd even be regarded as the primary outcome when the proportional hazard assumption fails.
rate research
Read More
Competing risks data are common in medical studies, and the sub-distribution hazard (SDH) ratio is considered an appropriate measure. However, because the limitations of hazard itself are not easy to interpret clinically and because the SDH ratio is valid only under the proportional SDH assumption, this article introduced an alternative index under competing risks, named restricted mean time lost (RMTL). Several test procedures were also constructed based on RMTL. First, we introduced the definition and estimation of RMTL based on Aalen-Johansen cumulative incidence functions. Then, we considered several combined tests based on the SDH and the RMTL difference (RMTLd). The statistical properties of the methods are evaluated using simulations and are applied to two examples. The type I errors of combined tests are close to the nominal level. All combined tests show acceptable power in all situations. In conclusion, RMTL can meaningfully summarize treatment effects for clinical decision making, and three combined tests have robust power under various conditions, which can be considered for statistical inference in real data analysis.
When considering a genetic disease with variable age at onset (ex: diabetes , familial amyloid neuropathy, cancers, etc.), computing the individual risk of the disease based on family history (FH) is of critical interest both for clinicians and patients. Such a risk is very challenging to compute because: 1) the genotype X of the individual of interest is in general unknown; 2) the posterior distribution P(X|FH, T > t) changes with t (T is the age at disease onset for the targeted individual); 3) the competing risk of death is not negligible. In this work, we present a modeling of this problem using a Bayesian network mixed with (right-censored) survival outcomes where hazard rates only depend on the genotype of each individual. We explain how belief propagation can be used to obtain posterior distribution of genotypes given the FH, and how to obtain a time-dependent posterior hazard rate for any individual in the pedigree. Finally, we use this posterior hazard rate to compute individual risk, with or without the competing risk of death. Our method is illustrated using the Claus-Easton model for breast cancer (BC). This model assumes an autosomal dominant genetic risk factor such as non-carriers (genotype 00) have a BC hazard rate $lambda$ 0 (t) while carriers (genotypes 01, 10 and 11) have a (much greater) hazard rate $lambda$ 1 (t). Both hazard rates are assumed to be piecewise constant with known values (cuts at 20, 30,. .. , 80 years). The competing risk of death is derived from the national French registry.
In the process of clinical diagnosis and treatment, the restricted mean survival time (RMST), which reflects the life expectancy of patients up to a specified time, can be used as an appropriate outcome measure. However, the RMST only calculates the mean survival time of patients within a period of time after the start of follow-up and may not accurately portray the change in a patients life expectancy over time. The life expectancy can be adjusted for the time the patient has already survived and defined as the conditional restricted mean survival time (cRMST). A dynamic RMST model based on the cRMST can be established by incorporating time-dependent covariates and covariates with time-varying effects. We analysed data from a study of primary biliary cirrhosis (PBC) to illustrate the use of the dynamic RMST model. The predictive performance was evaluated using the C-index and the prediction error. The proposed dynamic RMST model, which can explore the dynamic effects of prognostic factors on survival time, has better predictive performance than the RMST model. Three PBC patient examples were used to illustrate how the predicted cRMST changed at different prediction times during follow-up. The use of the dynamic RMST model based on the cRMST allows for optimization of evidence-based decision-making by updating personalized dynamic life expectancy for patients.
We apply Gaussian process (GP) regression, which provides a powerful non-parametric probabilistic method of relating inputs to outputs, to survival data consisting of time-to-event and covariate measurements. In this context, the covariates are regarded as the `inputs and the event times are the `outputs. This allows for highly flexible inference of non-linear relationships between covariates and event times. Many existing methods, such as the ubiquitous Cox proportional hazards model, focus primarily on the hazard rate which is typically assumed to take some parametric or semi-parametric form. Our proposed model belongs to the class of accelerated failure time models where we focus on directly characterising the relationship between covariates and event times without any explicit assumptions on what form the hazard rates take. It is straightforward to include various types and combinations of censored and truncated observations. We apply our approach to both simulated and experimental data. We then apply multiple output GP regression, which can handle multiple potentially correlated outputs for each input, to competing risks survival data where multiple event types can occur. By tuning one of the model parameters we can control the extent to which the multiple outputs (the time-to-event for each risk) are dependent thus allowing the specification of correlated risks. Simulation studies suggest that in some cases assuming dependence can lead to more accurate predictions.
Exposures to environmental chemicals during gestation can alter health status later in life. Most studies of maternal exposure to chemicals during pregnancy have focused on a single chemical exposure observed at high temporal resolution. Recent research has turned to focus on exposure to mixtures of multiple chemicals, generally observed at a single time point. We consider statistical methods for analyzing data on chemical mixtures that are observed at a high temporal resolution. As motivation, we analyze the association between exposure to four ambient air pollutants observed weekly throughout gestation and birth weight in a Boston-area prospective birth cohort. To explore patterns in the data, we first apply methods for analyzing data on (1) a single chemical observed at high temporal resolution, and (2) a mixture measured at a single point in time. We highlight the shortcomings of these approaches for temporally-resolved data on exposure to chemical mixtures. Second, we propose a novel method, a Bayesian kernel machine regression distributed lag model (BKMR-DLM), that simultaneously accounts for nonlinear associations and interactions among time-varying measures of exposure to mixtures. BKMR-DLM uses a functional weight for each exposure that parameterizes the window of susceptibility corresponding to that exposure within a kernel machine framework that captures non-linear and interaction effects of the multivariate exposure on the outcome. In a simulation study, we show that the proposed method can better estimate the exposure-response function and, in high signal settings, can identify critical windows in time during which exposure has an increased association with the outcome. Applying the proposed method to the Boston birth cohort data, we find evidence of a negative association between organic carbon and birth weight and that nitrate modifies the organic carbon, ...
Log in to be able to interact and post comments
comments
Fetching comments
Sign in to be able to follow your search criteria
