scholarly journals The Pseudo-Observation Analysis of Time-To-Event Data. Example from the Danish Diet, Cancer and Health Cohort Illustrating Assumptions, Model Validation and Interpretation of Results

2018 ◽  
Vol 7 (1) ◽  
Author(s):  
Lotte Maxild Mortensen ◽  
Camilla Plambeck Hansen ◽  
Kim Overvad ◽  
Søren Lundbye-Christensen ◽  
Erik T. Parner
Keyword(s):  
Cox Regression ◽  
Point Of View ◽  
Right Censoring ◽  
Event Analysis ◽  
Event Data ◽  
Time To Event ◽  
Time To Event Data ◽  
Model Control ◽  
Additive Risk ◽  
Observation Method

Abstract Regression analyses for time-to-event data are commonly performed by Cox regression. Recently, an alternative method, the pseudo-observation method, has been introduced. This method offers new possibilities of analyzing data exploring cumulative risks on both a multiplicative and an additive risk scale, in contrast to the multiplicative Cox regression model for hazard rates. Hence, the pseudo-observation method enables assessment of interaction on an additive scale. However, the pseudo-observation method implies more strict model assumptions regarding entry and censoring but avoids the assumption of proportional hazards (except from combined analyses of several time intervals where assumptions of constant hazard ratios, risk differences and relative risks may be imposed). Only few descriptions of the use of the method are accessible for epidemiologists. In this paper, we present the pseudo-observation method from a user-oriented point of view aiming at facilitating the use of this relatively new analytical tool. Using data from the Diet, Cancer and Health Cohort we give a detailed example of the application of the pseudo-observation method on time-to-event data with delayed entry and right censoring. We discuss model control and suggest analytic strategies when assumptions are not met. The introductory model control in the data example showed that data did not fulfill the assumptions of the pseudo-observation method. This was caused by selection of healthier participants at older baseline ages and a change in the distribution of study participants according to outcome risk during the inclusion period. Both selection effects need to be addressed in any time-to-event analysis and we show how these effects are accounted for in the pseudo-observation analysis. The pseudo-observation method provides us with a statistical tool which makes it possible to analyse cohort data on both multiplicative and additive risk scales including assessment of biological interaction on the risk difference scale. Thus, it might be a relevant choice of method – especially if the focus is to investigate interaction from a public health point of view.

scholarly journals Factorial analyses of treatment effects under independent right-censoring

2019 ◽  
Vol 29 (2) ◽  
pp. 325-343
Author(s):  
Dennis Dobler ◽  
Markus Pauly
Keyword(s):  
Asymptotic Properties ◽  
Small Sample ◽  
Right Censoring ◽  
Event Data ◽  
Time To Event ◽  
Sample Design ◽  
Time To Event Data ◽  
Practical Usefulness ◽  
Simulation Results ◽  
Special Case

This paper introduces new effect parameters for factorial survival designs with possibly right-censored time-to-event data. In the special case of a two-sample design, it coincides with the concordance or Wilcoxon parameter in survival analysis. More generally, the new parameters describe treatment or interaction effects and we develop estimates and tests to infer their presence. We rigorously study their asymptotic properties and additionally suggest wild bootstrapping for a consistent and distribution-free application of the inference procedures. The small sample performance is discussed based on simulation results. The practical usefulness of the developed methodology is exemplified on a data example about patients with colon cancer by conducting one- and two-factorial analyses.

scholarly journals Methods to Analyse Time-to-Event Data: The Kaplan-Meier Survival Curve

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Graziella D’Arrigo ◽  
Daniela Leonardis ◽  
Samar Abd ElHafeez ◽  
Maria Fusaro ◽  
Giovanni Tripepi ◽  
...  
Keyword(s):  
Survival Data ◽  
Molecular Mechanisms ◽  
Survival Curve ◽  
Interval Censoring ◽  
Right Censoring ◽  
Event Data ◽  
Time To Event ◽  
Time To Event Data ◽  
Kaplan Meier ◽  
Meier Survival Curve

Studies performed in the field of oxidative medicine and cellular longevity frequently focus on the association between biomarkers of cellular and molecular mechanisms of oxidative stress as well as of aging, immune function, and vascular biology with specific time to event data, such as mortality and organ failure. Indeed, time-to-event analysis is one of the most important methodologies used in clinical and epidemiological research to address etiological and prognostic hypotheses. Survival data require adequate methods of analyses. Among these, the Kaplan-Meier analysis is the most used one in both observational and interventional studies. In this paper, we describe the mathematical background of this technique and the concept of censoring (right censoring, interval censoring, and left censoring) and report some examples demonstrating how to construct a Kaplan-Meier survival curve and how to apply this method to provide an answer to specific research questions.

scholarly journals A univariable and multivariable analysis of time-to-event data based on restricted mean survival time: A combination with traditional survival methods.

2019 ◽  
Author(s):  
Qiao Huang ◽  
Jun Lyv ◽  
Bing-hui Li ◽  
Lin-lu Ma ◽  
Tong Deng ◽  
...  
Keyword(s):  
Survival Time ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Hazard Ratio ◽  
Event Data ◽  
Time To Event ◽  
Mean Survival Time ◽  
Time To Event Data ◽  
Effect Measure ◽  
Restricted Mean Survival Time

Abstract Background Hazard ratio is considered as an appropriate effect measure of time-to-event data. However, hazard ratio is only valid when proportional hazards (PH) assumption is met. The use of the restricted mean survival time (RMST) is proposed and recommended without limitation of PH assumption. Method 4405 osteosarcomas were captured from Surveillance, Epidemiology and End Results Program Database. Traditional survival analyses and RMST-based analyses were integrated into a flowchart and applied for univariable and multivariable analyses, using hazard ratio (HR) and difference in RMST (survival time lost or gain, STL or STG) as effect measures. The relationship between difference in RMST and HR were explored when PH assumption was and was not met, respectively. Results In univariable analyses, using difference in RMST calculated by Kaplan-Meier methods as reference, pseudo-value regressions (R2=0.99) and inverse probability of censoring probability (IPCW) regressions with group-specific weights (R2=1.00) provided more consistent estimation on difference in RMST than IPCW with individual weights (R2=0.09). In multivariable analysis, age (HR:1.03, STL: 3.86 months), diagnosis in 1970~1980s (HR:1.39 STL:27.49 months), metastasis (HR:4.47, STL: 202 months), surgery (HR:0.58, SLG:35.55 months) and radiation (HR:1.46, SLT:44.65 months), met PH assumption and were main independent factors for overall survival. In both univariable and multivariable variables, a robust negative logarithmic linear relationship between HRs estimated by Cox regression and differences in RMST by pseudo-value regressions was only observed when PH assumption was hold (Difference in RMST = -109.3✕ln (HR) - 0.83, R² = 0.97, and Difference = -127.7✕ln (HR) – 9.49, R² = 0.93, respectively.) Conclusion The flowchart will be intuitive and helpful to instruct appropriate use of RMST based and traditional methods. RMST-based methods provided an absolute effect measure to inspect effects of covariates on survival time and promote evidence communication with HR. Difference in RMST should be reported with hazard ratio routinely.

scholarly journals A univariable and multivariable analysis of right censored time-to-event data based on restricted mean survival time: A combination with traditional survival methods.

2020 ◽  
Author(s):  
Qiao Huang ◽  
Jun Lyv ◽  
Bing-hui Li ◽  
Lin-lu Ma ◽  
Tong Deng ◽  
...  
Keyword(s):  
Survival Time ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Hazard Ratio ◽  
Event Data ◽  
Time To Event ◽  
Mean Survival Time ◽  
Time To Event Data ◽  
Effect Measure ◽  
Restricted Mean Survival Time

Abstract Background Hazard ratio is considered as an appropriate effect measure of time-to-event data. However, hazard ratio is only valid when proportional hazards (PH) assumption is met. The use of the restricted mean survival time (RMST) is proposed and recommended without limitation of PH assumption. Method 4405 osteosarcomas were captured from Surveillance, Epidemiology and End Results Program Database. Traditional survival analyses and RMST-based analyses were integrated into a flowchart and applied for univariable and multivariable analyses, using hazard ratio (HR) and difference in RMST (survival time lost or gain, STL or STG) as effect measures. The relationship between difference in RMST and HR were explored when PH assumption was and was not met, respectively. Results In group comparison and univariable regressions, using difference in RMST calculated by Kaplan-Meier methods as reference, pseudo-value regressions (R2=0.99) and inverse probability of censoring probability (IPCW) regressions with group-specific weights (R2=1.00) provided more consistent estimation on difference in RMST than IPCW with individual weights (R2=0.09). In multivariable analysis, age (HR:1.03, STL: 3.86 months), diagnosis in 1970~1980s (HR:1.39 STL:27.49 months), metastasis (HR:4.47, STL: 202 months), surgery (HR:0.58, SLG:35.55 months) and radiation (HR:1.46, SLT:44.65 months) met PH assumption and were main independent factors for overall survival. In both univariable and multivariable variables, a robust negative logarithmic linear relationship between HRs estimated by Cox regression and differences in RMST by pseudo-value regressions was only observed when PH assumption was hold. Conclusion The flowchart will be intuitive and helpful to instruct appropriate use of RMST based and traditional methods. RMST-based methods provided an absolute effect measure to inspect effects of covariates on survival time and promote evidence communication with HR. Difference in RMST should be reported with hazard ratio routinely.

Approximate Bayesian inference for joint linear and partially linear modeling of longitudinal zero-inflated count and time to event data

2021 ◽  
pp. 096228022110028
Author(s):  
T Baghfalaki ◽  
M Ganjali
Keyword(s):  
Linear Model ◽  
Joint Modeling ◽  
Partially Linear Model ◽  
Event Data ◽  
Time To Event ◽  
Data Set ◽  
Partially Linear ◽  
Time To Event Data ◽  
Count Response ◽  
Approximate Bayesian

Joint modeling of zero-inflated count and time-to-event data is usually performed by applying the shared random effect model. This kind of joint modeling can be considered as a latent Gaussian model. In this paper, the approach of integrated nested Laplace approximation (INLA) is used to perform approximate Bayesian approach for the joint modeling. We propose a zero-inflated hurdle model under Poisson or negative binomial distributional assumption as sub-model for count data. Also, a Weibull model is used as survival time sub-model. In addition to the usual joint linear model, a joint partially linear model is also considered to take into account the non-linear effect of time on the longitudinal count response. The performance of the method is investigated using some simulation studies and its achievement is compared with the usual approach via the Bayesian paradigm of Monte Carlo Markov Chain (MCMC). Also, we apply the proposed method to analyze two real data sets. The first one is the data about a longitudinal study of pregnancy and the second one is a data set obtained of a HIV study.

scholarly journals Mitigation of biases in estimating hazard ratios under non-sensitive and non-specific observation of outcomes–applications to influenza vaccine effectiveness

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Ulrike Baum ◽  
Sangita Kulathinal ◽  
Kari Auranen
Keyword(s):  
False Positive ◽  
False Positive Rate ◽  
Vaccine Effectiveness ◽  
Partial Likelihood ◽  
Event Data ◽  
Time To Event ◽  
Positive Events ◽  
Time To Event Data ◽  
Hazard Ratios ◽  
Positive Rate

Abstract Background Non-sensitive and non-specific observation of outcomes in time-to-event data affects event counts as well as the risk sets, thus, biasing the estimation of hazard ratios. We investigate how imperfect observation of incident events affects the estimation of vaccine effectiveness based on hazard ratios. Methods Imperfect time-to-event data contain two classes of events: a portion of the true events of interest; and false-positive events mistakenly recorded as events of interest. We develop an estimation method utilising a weighted partial likelihood and probabilistic deletion of false-positive events and assuming the sensitivity and the false-positive rate are known. The performance of the method is evaluated using simulated and Finnish register data. Results The novel method enables unbiased semiparametric estimation of hazard ratios from imperfect time-to-event data. False-positive rates that are small can be approximated to be zero without inducing bias. The method is robust to misspecification of the sensitivity as long as the ratio of the sensitivity in the vaccinated and the unvaccinated is specified correctly and the cumulative risk of the true event is small. Conclusions The weighted partial likelihood can be used to adjust for outcome measurement errors in the estimation of hazard ratios and effectiveness but requires specifying the sensitivity and the false-positive rate. In absence of exact information about these parameters, the method works as a tool for assessing the potential magnitude of bias given a range of likely parameter values.

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