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A GMM approach in coupling internal data and external summary information with heterogeneous data populations

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Science China Mathematics 2024年第5期67卷 1115-1132页

作者： Jun Shao Jinyi Wang Lei Wang Key Laboratory of Advanced Theory and Application in Statistics and Data Science(East China Normal University) Ministry of EducationShanghai 200062China School of Statistics East China Normal UniversityShanghai 200062China Department of Statistics University of Wisconsin-MadisonWI 53706USA School of Statistics and Data Science KLMDASRLEBPS and LPMCNankai UniversityTianjin 300071China

Because of advances in data collection and storage,statistical analysis in modern scientific research and practice now has opportunities to utilize external information such as summary statistics from similar studies.A likelihood approach based on a parametric model assumption has been developed in the literature to utilize external summary information when the populations for external and main internal data are assumed to be the same.In this article,we instead consider the generalized estimation equation(GEE)approach for statistical inference,which is semiparametric or nonparametric,and show how to utilize external summary information even when internal and external data populations are not the same.Our approach is coupling the internal data and external summary information to form additional estimation equations and then applying the generalized method of moments(GMM).We show that the proposed GMM estimator is asymptotically normal and,under some conditions,is more efficient than the GEE estimator without using external summary information.Estimators of the asymptotic covariance matrix of the GMM estimators are also proposed.Simulation results are obtained to confirm our theory and quantify the improvements by utilizing external data.An example is also included for illustration.

关键词： adjustment for heterogeneity constraint data integration generalized method of moments summarystatistic

Nonignorable item nonresponse in panel data

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Statistical Theory and Related Fields 2022年第1期6卷 58-71页

作者： Sijing Li Jun Shao Department of Statistics University of Wisconsin-MadisonMadisonWIUSA

To estimate unknown population parameters based on panel data having nonignorable item nonresponse,we propose an innovative data grouping approach according to the number of observed components in the multivariate outcome y when the joint distribution of y and asso-ciated covariate x is nonparametric and the nonresponse probability conditional on y and x has a parametric form.To deal with the identifiability issue,we utilise a nonresponse instrument 2,an auxiliary variable related to y but not related to the nonresponse probability conditional ony and x.We apply a modified generalised method of moments to obtain estimators of the param-eters in the nonresponse probability,and a generalised regression estimation to utilise covariate information for efficient estimation of population parameters.Consistency and asymptotic nor-mality of the proposed estimators of the population parameters are established.Simulation and real data results are presented.

关键词： Cluster sampling generalised regression grouping homogeneity multivariate outcome

Inference after covariate-adaptive randomisation:aspects of methodology and theory

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Statistical Theory and Related Fields 2021年第3期5卷 172-186页

作者： Jun Shao KLATASDS-MOE School of StatisticsEast China Normal UniversityShanghaiPeople’s Republic of China Department of Statistics University ofWisconsin-MadisonMadisonWIUSA

Covariate-adaptive randomisation has a more than 45 years of history of applications in clinical trials,in order to balance treatment assignments across prognostic factors that may have influence on the outcomes of interest.However,almost no theory had been developed for covariate-adaptive randomisation until a paper on the theory of testing hypotheses published in 2010.In this article,we review aspects of methodology and theory developed in the last decade for statistical inference under covariate-adaptive randomisation.Wefocus on issues such as whether a conventional procedure valid under the assumption that treatments are assigned completely at random is still valid or conservative when the actual randomisation is covariateadaptive,how a valid inference procedure can be obtained by modifying a conventional method or directly constructed by stratifying the covariates used in randomisation,whether inference procedures have different properties when covariate-adaptive randomisation schemes have different degrees of balancing assignments,and how to further adjust covariates in the inference procedures to gain more efficiency.Recommendations are made during the review and further research problems are discussed.

关键词： balancedness of assignments efficiency model-assisted approach model free inference stratification survival analysis

Rejoinder on‘Inference after covariate-adaptive randomization:aspects of methodology and theory’

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Statistical Theory and Related Fields 2021年第3期5卷 196-199页

作者： Jun Shao KLATASDS-MOE School of StatisticsEast China Normal UniversityShanghaiPeople’s Republic of China Department of Statistics University of Wisconsin-MadisonMadisonWIUSA

I would like to thank all discussants for their insightful discussions on the topic of statistical inference after covariate-adaptive randomisation,especially for including reviews of some new results and references that are not in my review written more than a year ago.I hope these discussions together with my review will stimulate further studies in this important area having many applications particularly in clinical trials.

关键词： discussions thank insight

Robust variance estimation for covariate-adjusted unconditional treatment effect in randomized clinical trials with binary outcomes

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Statistical Theory and Related Fields 2023年第2期7卷 159-163页

作者： Ting Ye Marlena Bannick Yanyao Yi Jun Shao Department of Biostatistics University of WashingtonSeattleWAUSA Global Statistical Sciences Eli Llly and CompanyIndianapolisINUSA School of Statistics East China Normal UniversityShanghaiPeople's Republic of China Department of Statistics University of WisconsinMadisonWIUSA

To improve the precision of estimation and power of testing hypothesis for an unconditional treatment effect in randomized clinical trials with binary outcomes,researchers and regulatory agencies recommend using g computation as a reliable method of covariate adjustment.How-ever,the practical application of g-computation is hindered by the lack of an explicit robust variance formula that can be used for different unconditional treatment effects of interest.To fill this gap,we provide explicit and robust variance estimators for g-computation estimators and demonstrate through simulations that the variance estimators can be reliably applied in practice.

关键词： G-computation modelassisted nonlinear covariate adjustment risk difference logistic regression standardization

Negative effects of transthyretin in high myopic vitreous on diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2017年第12期10卷 1864-1869页

作者： Jun Shao Yong Yao Departm ent of Ophthalmology W uxi People’s Hospital Aflicted to Nanjing Medical UniversityWuxi 214023Jiangsu ProvinceChina

AIM：To analyze the relationship between vitreous transthyretin（TTR） levels,high myopia and diabetic retinopathy（DR）.METHODS：We selected 6722 individuals from the southern Jiangsu Province for diabetes and ophthalmic examinations.The TTR concentration in the vitreous of 50 patients with high myopia and diabetes,50 patients with only DR,and 20 healthy controls were determined by ELISA.Key factors in Tie2 pathway in DR development including vascular endothecial growth factor（VEGF）,Tie2,Angpt1,Angpt2,vascular endothelial growth factor receptor（VEGFR） 1 and VEGFR2 were also detected by ELISA.RESULTS：The prevalence of DR in patients with diabetes and myopia [〈6.00 diopter（D）],diabetes and high myopia（〉6.00 D）,and diabetes without myopia were 11.1%,2.5%,and 60.0%,respectively.The vitreous TTR concentration of patients with diabetes and high myopia was approximately 6.5-and 4.2-times higher than those of patients with DR and healthy controls,respectively（P〈0.05）.Following the vitreous TTR concentration,the levels of VEGF,Tie2,Angpt1,Angpt2,VEGFR1 and VEGFR2 in vitreous of diabetes and high myopia patients,DR patients and healthy controls were detected as dramatically fluctuated.CONCLUSION：The results suggest that TTR can affect the vitreous contents of key factors in Tie2 pathway for neovascularization,and there should be a protective association between abundant TTR levels in the vitreous of highly myopic patients and a decreased risk of DR.

关键词： transthyretin diabetic retinopathy highmyopia protective

Repression of retinal microvascular endothelial cells by transthyretin under simulated diabetic retinopathy conditions

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International Journal of Ophthalmology(English edition) 2016年第6期9卷 809-815页

作者： Jun Shao Yong Yao Department of Ophthalmology Wuxi People's Hospital Affiliated to Nanjing Medical University

AIM： To investigate biological effects of transthyretin （TTR） on the development of neovascularization under simulated diabetic retinopathy （DR） condition associated with high glucose and hypoxia. METHODS： Human retinal microvascular endothelial cells （hRECs） were cultured in normal and simulated DR environments with high glucose and hypoxia. The normal serum glucose concentration is approximately 5.5 mmol/L; thus, hyperglycemia was simulated with 25 mmol/L glucose, while hypoxia was induced using 200 μmol/L CoCI. The influence of TTR on hRECs and human retinal pigment epithelial cells （hRPECs） was determined by incubating the cells with 4μmol/L TTR in normal and abnormal media. A co -culture system was then employed to evaluate the effects of hRPECs on hRECs. RESULTS： Decreased hRECs and hRPECs were observed under abnormal conditions, including high- glucose and hypoxic media. In addition, hRECs were significantly inhibited by 4 pmol/L exogenous TTR during hyperglycemic culture. During co-culture, hRPECs inhibited hRECs in both the normal and abnormal environments. CONCLUSION： hREC growth is inhibited by exogenous TTR under simulated DR environments with highglucose and hypoxic, particularly in the medium containing 25 mmol/L glucose, hRPECs, which manufacture TTR in the eye, also represses hRECs in the same environment. TTR is predicted to inhibit the proliferation of hRECs and neovascularization.

关键词： transthyretin diabetic retinal human retinalmicrovascular endothelial cells human retinal pigmentepithelial cells hyperglycemia hypoxia

Meta-analysis of independent datasets using constrained generalised method of moments

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Statistical Theory and Related Fields 2020年第1期4卷 109-116页

作者： Menghao Xu Jun Shao KLATASDS-MOE School of StatisticsEast China Normal UniversityShanghaiPeople’s Republic of China Department of Statistics University of Wisconsin-MadisonMadisonWIUSA

Wepropose a constrained generalised method of moments(CGMM)for enhancing the efficiency of estimators in meta-analysis in which some studies do not measure all covariates associated with the response or outcome.Under some assumptions,weshow that the proposedCGMMestimators have good asymptotic properties.Wealso demonstrate the effectiveness of the proposed method through simulation studies with fixed sample sizes.

关键词： Meta-analysis generalised method of moments efficiency

A GMM approach in coupling internal data and external summary information with heterogeneous data populations

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Science China Mathematics 2023年

作者： Jun Shao Jinyi Wang Lei Wang School of Statistics and Data Science KLMDASR LEBPS and LPMC Nankai University Key Laboratory of Advanced Theory and Application in Statistics and Data Science (East China Normal University) Ministry of Education Department of Statistics University of Wisconsin-Madison School of Statistics East China Normal University

Because of advances in data collection and storage, statistical analysis in modern scientific research and practice now has opportunities to utilize external information such as summary statistics from similar studies. A likelihood approach based on a parametric model assumption has been developed in the literature to utilize external summary information when the populations for the external data and main internal data are assumed to be the same. In this article, we instead consider the generalized estimation equation (GEE)approach for statistical inference, which is semiparametric or nonparametric, and show how to utilize external summary information even when internal and external data populations are not the same. Our approach is coupling the internal data and external summary information to form additional estimation equations and then applying the generalized method of moments (GMM). We show that the proposed GMM estimator is asymptotically normal and, under some conditions, is more efficient than the GEE estimator without using external summary information. Estimators of the asymptotic covariance matrix of the GMM estimators are also proposed. Simulation results are obtained to confirm our theory and quantify the improvements by utilizing external data. An example is also included for illustration.

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