Journal ArticleDOI
Changepoint inference in the presence of missing covariates for principal surrogate evaluation in vaccine trials
Tao Yang,Ying Huang,Youyi Fong +2 more
TLDR
A regression methodology that allows joint estimation of all model parameters as well as a two-step method that separates the estimation of the threshold parameter from the rest of the parameters is developed and the asymptotic properties of the proposed estimators are established.Abstract:
We consider the use of threshold-based regression models for evaluating immune response biomarkers as principal surrogate markers of a vaccine's protective effect. Threshold-based regression models, which allow the relationship between a clinical outcome and a covariate to change dramatically across a threshold value in the covariate, have been studied by various authors under fully observed data. Limited research, however, has examined these models in the presence of missing covariates, such as the counterfactual potential immune responses of a participant in the placebo arm of a standard vaccine trial had s/he been assigned to the vaccine arm instead. Based on a hinge model for a threshold effect of the principal surrogate on vaccine efficacy, we develop a regression methodology that consists of two components: (1) The estimated likelihood method is employed to handle missing potential outcomes, and (2) a penalty is imposed on the estimated likelihood to ensure satisfactory finite sample performance. We develop a method that allows joint estimation of all model parameters as well as a two-step method that separates the estimation of the threshold parameter from the rest of the parameters. Stable iterative algorithms are developed to implement the two methods and the asymptotic properties of the proposed estimators are established. In simulation studies, the proposed estimators are shown to have satisfactory finite sample performance. The proposed methods are applied to analyze a real dataset collected from dengue vaccine efficacy trials to predict how vaccine efficacy varies with an individual's potential immune response if receiving vaccine.read more
Citations
More filters
Posted Content
Online network change point detection with missing values.
Paromita Dubey,Haotian Xu,Yi Yu +2 more
TL;DR: In this article, a polynomial-time change point detection algorithm was proposed for dynamic networks with heterogeneous missing pattern across the networks and the time course, where the missingness probabilities, the networks' entrywise sparsity, the rank of the networks, and the jump size in terms of the Frobenius norm, are all allowed to vary as functions of the pre-change sample size.
References
More filters
Journal ArticleDOI
Bias reduction of maximum likelihood estimates
TL;DR: In this paper, the first-order term is removed from the asymptotic bias of maximum likelihood estimates by a suitable modification of the score function, and the effect is to penalize the likelihood by the Jeffreys invariant prior.
Journal ArticleDOI
Principal stratification in causal inference.
TL;DR: This work proposes a general framework for comparing treatments adjusting for posttreatment variables that yields principal effects based on principal stratification and attacks the problem of surrogate or biomarker endpoints, where all current definitions of surrogacy do not generally have the desired interpretation as causal effects of treatment on outcome.
Journal ArticleDOI
Correlates of Protection Induced by Vaccination
TL;DR: This paper attempts to summarize current knowledge about immune responses to vaccines that correlate with protection, finding some vaccines have no true correlates, but only useful surrogates, for an unknown protective response.
Journal ArticleDOI
On the existence of maximum likelihood estimates in logistic regression models
Adelin Albert,Ja. Anderson +1 more
TL;DR: For multinomial logistic regression models, this article proved existence theorems by considering the possible patterns of data points, which fall into three mutually exclusive and exhaustive categories: complete separation, quasicomplete separation and overlap.
Journal ArticleDOI
Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial
Maria Rosario Capeding,Ngoc Huu Tran,Sri Rezeki Hadinegoro,Hussain Imam Muhammad Ismail,Tawee Chotpitayasunondh,Mary Noreen Chua,Chan Quang Luong,Kusnandi Rusmil,Dewa Nyoman Wirawan,Revathy Nallusamy,Punnee Pitisuttithum,Usa Thisyakorn,In-Kyu Yoon,Diane van der Vliet,Edith Langevin,Thelma Laot,Yanee Hutagalung,Carina Frago,Mark Boaz,T. Anh Wartel,Nadia Tornieporth,Melanie Saville,Alain Bouckenooghe +22 more
TL;DR: The findings show that dengue vaccine is efficacious when given as three injections at months 0, 6, and 12 to children aged 2-14 years in endemic areas in Asia, and has a good safety profile.