A1-3: The Performance of Propensity Score Methods for Estimating Hazard Ratio in Time-to-Event Data

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.

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

10.21203/rs.2.18724/v2 ◽

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.

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Bayesian design of clinical trials using joint models for longitudinal and time-to-event data

Biostatistics ◽

10.1093/biostatistics/kxaa044 ◽

2020 ◽

Author(s):

Jiawei Xu ◽

Matthew A Psioda ◽

Joseph G Ibrahim

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Hazard Ratio ◽

Type I ◽

Event Data ◽

Time To Event ◽

Joint Models ◽

Modeling Framework ◽

Time To Event Data ◽

Longitudinal Outcome

Summary Joint models for longitudinal and time-to-event data are increasingly used for the analysis of clinical trial data. However, few methods have been proposed for designing clinical trials using these models. In this article, we develop a Bayesian clinical trial design methodology focused on evaluating the treatment’s effect on the time-to-event endpoint using a flexible trajectory joint model. By incorporating the longitudinal outcome trajectory into the hazard model for the time-to-event endpoint, the joint modeling framework allows for non-proportional hazards (e.g., an increasing hazard ratio over time). Inference for the time-to-event endpoint is based on an average of a time-varying hazard ratio which can be decomposed according to the treatment’s direct effect on the time-to-event endpoint and its indirect effect, mediated through the longitudinal outcome. We propose an approach for sample size determination for a trial such that the design has high power and a well-controlled type I error rate with both operating characteristics defined from a Bayesian perspective. We demonstrate the methodology by designing a breast cancer clinical trial with a primary time-to-event endpoint and where predictive longitudinal outcome measures are also collected periodically during follow-up.

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Prognostic review and time-to-event data meta-analysis of low skeletal muscle mass in patients with peripheral arterial disease of the lower limbs undergoing revascularization

International Angiology ◽

10.23736/s0392-9590.19.04248-2 ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Madeleine Sharpe ◽

Emeka Okoye ◽

George A. Antoniou

Keyword(s):

Skeletal Muscle ◽

Peripheral Arterial Disease ◽

Skeletal Muscle Mass ◽

Meta Analysis ◽

Arterial Disease ◽

Lower Limbs ◽

Event Data ◽

Time To Event ◽

Time To Event Data ◽

Peripheral Arterial

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

Statistical Methods in Medical Research ◽

10.1177/09622802211002868 ◽

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.

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

Emerging Themes in Epidemiology ◽

10.1186/s12982-020-00091-z ◽

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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