Classical survival analysis assumes all subjects will experience the event of interest, but in some cases, a portion of the population may never encounter the event. These survival methods further assume independent s...Classical survival analysis assumes all subjects will experience the event of interest, but in some cases, a portion of the population may never encounter the event. These survival methods further assume independent survival times, which is not valid for honey bees, which live in nests. The study introduces a semi-parametric marginal proportional hazards mixture cure (PHMC) model with exchangeable correlation structure, using generalized estimating equations for survival data analysis. The model was tested on clustered right-censored bees survival data with a cured fraction, where two bee species were subjected to different entomopathogens to test the effect of the entomopathogens on the survival of the bee species. The Expectation-Solution algorithm is used to estimate the parameters. The study notes a weak positive association between cure statuses (ρ1=0.0007) and survival times for uncured bees (ρ2=0.0890), emphasizing their importance. The odds of being uncured for A. mellifera is higher than the odds for species M. ferruginea. The bee species, A. mellifera are more susceptible to entomopathogens icipe 7, icipe 20, and icipe 69. The Cox-Snell residuals show that the proposed semiparametric PH model generally fits the data well as compared to model that assume independent correlation structure. Thus, the semi parametric marginal proportional hazards mixture cure is parsimonious model for correlated bees survival data.展开更多
As cancer therapy has progressed dramatically, its goal has shifted toward cure of the disease (curative therapy) rather than prolongation of time to death (life-prolonging therapy). Consequently, the proportion of cu...As cancer therapy has progressed dramatically, its goal has shifted toward cure of the disease (curative therapy) rather than prolongation of time to death (life-prolonging therapy). Consequently, the proportion of cured patients (c) has become an important measure of the long-term survival benefit derived from therapy. In 1949, Boag addressed this issue by developing the parametric log-normal cure model, which provides estimates of c and m where m is the mean of log times to death from cancer among uncured patients. Unfortunately, traditional methods based on the proportional hazards model like the Cox regression and log-rank tests cannot provide an estimate of either c or m. Rather, these methods estimate only the differences in hazard between two or more groups. In order to evaluate the long-term validity and usefulness of the parametric cure model compared with the proportional hazards model, we reappraised randomized controlled trials and simulation studies of breast cancer and other malignancies. The results reveal that: 1) the traditional methods fail to distinguish between curative and life-prolonging therapies;2) in certain clinical settings, these methods may favor life-prolonging treatment over curative treatment, giving clinicians a false estimate of the best regimen;3) although the Boag model is less sensitive to differences in failure time when follow-up is limited, it gains power as more failures occur. In conclusion, unless the disease is always fatal, the primary measure of survival benefit should be c rather than m or hazard ratio. Thus, the Boag lognormal cure model provides more accurate and more useful insight into the long-term benefit of cancer treatment than the traditional alternatives.展开更多
In some situations,the failure time of interest is defined as the gap time between two related events and the observations on both event times can suffer either right or interval censoring.Such data are usually referr...In some situations,the failure time of interest is defined as the gap time between two related events and the observations on both event times can suffer either right or interval censoring.Such data are usually referred to as doubly censored data and frequently encountered in many clinical and observational studies.Additionally,there may also exist a cured subgroup in the whole population,which means that not every individual under study will experience the failure time of interest eventually.In this paper,we consider regression analysis of doubly censored data with a cured subgroup under a wide class of flexible transformation cure models.Specifically,we consider marginal likelihood estimation and develop a two-step approach by combining the multiple imputation and a new expectation-maximization(EM)algorithm for its implementation.The resulting estimators are shown to be consistent and asymptotically normal.The finite sample performance of the proposed method is investigated through simulation studies.The proposed method is also applied to a real dataset arising from an AIDS cohort study for illustration.展开更多
The mixture cure model is the most popular model used to analyse the major event with a potential cure fraction.But in the real world there may exist a potential risk from other non-curable competing events.In this pa...The mixture cure model is the most popular model used to analyse the major event with a potential cure fraction.But in the real world there may exist a potential risk from other non-curable competing events.In this paper,we study the accelerated failure time model with mixture cure model via kernel-based nonparametric maximum likelihood estimation allowing non-curable competing risk.An EM algorithm is developed to calculate the estimates for both the regression parameters and the unknown error densities,in which a kernel-smoothed conditional profile likelihood is maximised in the M-step,and the resulting estimates are consistent.Its performance is demonstrated through comprehensive simulation studies.Finally,the proposed method is applied to the colorectal clinical trial data.展开更多
文摘Classical survival analysis assumes all subjects will experience the event of interest, but in some cases, a portion of the population may never encounter the event. These survival methods further assume independent survival times, which is not valid for honey bees, which live in nests. The study introduces a semi-parametric marginal proportional hazards mixture cure (PHMC) model with exchangeable correlation structure, using generalized estimating equations for survival data analysis. The model was tested on clustered right-censored bees survival data with a cured fraction, where two bee species were subjected to different entomopathogens to test the effect of the entomopathogens on the survival of the bee species. The Expectation-Solution algorithm is used to estimate the parameters. The study notes a weak positive association between cure statuses (ρ1=0.0007) and survival times for uncured bees (ρ2=0.0890), emphasizing their importance. The odds of being uncured for A. mellifera is higher than the odds for species M. ferruginea. The bee species, A. mellifera are more susceptible to entomopathogens icipe 7, icipe 20, and icipe 69. The Cox-Snell residuals show that the proposed semiparametric PH model generally fits the data well as compared to model that assume independent correlation structure. Thus, the semi parametric marginal proportional hazards mixture cure is parsimonious model for correlated bees survival data.
文摘As cancer therapy has progressed dramatically, its goal has shifted toward cure of the disease (curative therapy) rather than prolongation of time to death (life-prolonging therapy). Consequently, the proportion of cured patients (c) has become an important measure of the long-term survival benefit derived from therapy. In 1949, Boag addressed this issue by developing the parametric log-normal cure model, which provides estimates of c and m where m is the mean of log times to death from cancer among uncured patients. Unfortunately, traditional methods based on the proportional hazards model like the Cox regression and log-rank tests cannot provide an estimate of either c or m. Rather, these methods estimate only the differences in hazard between two or more groups. In order to evaluate the long-term validity and usefulness of the parametric cure model compared with the proportional hazards model, we reappraised randomized controlled trials and simulation studies of breast cancer and other malignancies. The results reveal that: 1) the traditional methods fail to distinguish between curative and life-prolonging therapies;2) in certain clinical settings, these methods may favor life-prolonging treatment over curative treatment, giving clinicians a false estimate of the best regimen;3) although the Boag model is less sensitive to differences in failure time when follow-up is limited, it gains power as more failures occur. In conclusion, unless the disease is always fatal, the primary measure of survival benefit should be c rather than m or hazard ratio. Thus, the Boag lognormal cure model provides more accurate and more useful insight into the long-term benefit of cancer treatment than the traditional alternatives.
基金Supported by the National Natural Science Foundation of China(Grant Nos.11771431,11690015,11926341,11901128 and 11601097)Key Laboratory of RCSDS,CAS(Grant Nos.2008DP 173182)Natural Science Foundation of Guangdong Province of China(Grant No.2018A030310068)。
文摘In some situations,the failure time of interest is defined as the gap time between two related events and the observations on both event times can suffer either right or interval censoring.Such data are usually referred to as doubly censored data and frequently encountered in many clinical and observational studies.Additionally,there may also exist a cured subgroup in the whole population,which means that not every individual under study will experience the failure time of interest eventually.In this paper,we consider regression analysis of doubly censored data with a cured subgroup under a wide class of flexible transformation cure models.Specifically,we consider marginal likelihood estimation and develop a two-step approach by combining the multiple imputation and a new expectation-maximization(EM)algorithm for its implementation.The resulting estimators are shown to be consistent and asymptotically normal.The finite sample performance of the proposed method is investigated through simulation studies.The proposed method is also applied to a real dataset arising from an AIDS cohort study for illustration.
基金supported by the Natural Science Foundation of China(Nos.11271136,81530086)the 111 Project of China(No.B14019).
文摘The mixture cure model is the most popular model used to analyse the major event with a potential cure fraction.But in the real world there may exist a potential risk from other non-curable competing events.In this paper,we study the accelerated failure time model with mixture cure model via kernel-based nonparametric maximum likelihood estimation allowing non-curable competing risk.An EM algorithm is developed to calculate the estimates for both the regression parameters and the unknown error densities,in which a kernel-smoothed conditional profile likelihood is maximised in the M-step,and the resulting estimates are consistent.Its performance is demonstrated through comprehensive simulation studies.Finally,the proposed method is applied to the colorectal clinical trial data.
