We consider the situation where there is a known regression model that can be used to predict an outcome,
We consider a situation where rich historical data are available for the coefficients and their standard errors in an established regression model describing the association between a binary outcome variable Y and a set of predicting factors X, from a large study. We would like to utilize this summary information for improving estimation and prediction in an expanded model of interest, Y|X,B. The additional variable B is a new biomarker, measured on a small number of subjects in a new data set. We develop and evaluate several approaches for translating the external information into constraints on regression coefficients in a logistic regression model of Y|X,B. Borrowing from the measurement error literature we establish an approximate relationship between the regression coefficients in the models Pr(Y=1|X,β), Pr(Y=1|X,B,γ) and E(B|X,θ) for a Gaussian distribution of B. For binary B we propose an alternative expression. The simulation results comparing these methods indicate that historical information on Pr(Y=1|X,β) can improve the efficiency of estimation and enhance the predictive power in the regression model of interest Pr(Y=1|X,B,γ). We illustrate our methodology by enhancing the high grade prostate cancer prevention trial risk calculator, with two new biomarkers: prostate cancer antigen 3 and TMPRSS2:ERG.
more » « less- PAR ID:
- 10398888
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Journal of the Royal Statistical Society Series C: Applied Statistics
- Volume:
- 68
- Issue:
- 1
- ISSN:
- 0035-9254
- Page Range / eLocation ID:
- p. 121-139
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
<italic>Abstract</italic> Y , from a set of predictor variablesX . A new variableB is expected to enhance the prediction ofY . A dataset of sizen containingY ,X andB is available, and the challenge is to build an improved model forY |X ,B that uses both the available individual level data and some summary information obtained from the known model forY |X . We propose a synthetic data approach, which consists of creatingm additional synthetic data observations, and then analyzing the combined dataset of sizen +m to estimate the parameters of theY |X ,B model. This combined dataset of sizen +m now has missing values ofB form of the observations, and is analyzed using methods that can handle missing data (e.g., multiple imputation). We present simulation studies and illustrate the method using data from the Prostate Cancer Prevention Trial. Though the synthetic data method is applicable to a general regression context, to provide some justification, we show in two special cases that the asymptotic variances of the parameter estimates in theY |X ,B model are identical to those from an alternative constrained maximum likelihood estimation approach. This correspondence in special cases and the method's broad applicability makes it appealing for use across diverse scenarios.The Canadian Journal of Statistics 47: 580–603; 2019 © 2019 Statistical Society of Canada -
more » « less
Summary Comparative effectiveness research often involves evaluating the differences in the risks of an event of interest between two or more treatments using observational data. Often, the post‐treatment outcome of interest is whether the event happens within a pre‐specified time window, which leads to a binary outcome. One source of bias for estimating the causal treatment effect is the presence of confounders, which are usually controlled using propensity score‐based methods. An additional source of bias is right‐censoring, which occurs when the information on the outcome of interest is not completely available due to dropout, study termination, or treatment switch before the event of interest. We propose an inverse probability weighted regression‐based estimator that can simultaneously handle both confounding and right‐censoring, calling the method CIPWR, with the letter C highlighting the censoring component. CIPWR estimates the average treatment effects by averaging the predicted outcomes obtained from a logistic regression model that is fitted using a weighted score function. The CIPWR estimator has a double robustness property such that estimation consistency can be achieved when either the model for the outcome or the models for both treatment and censoring are correctly specified. We establish the asymptotic properties of the CIPWR estimator for conducting inference, and compare its finite sample performance with that of several alternatives through simulation studies. The methods under comparison are applied to a cohort of prostate cancer patients from an insurance claims database for comparing the adverse effects of four candidate drugs for advanced stage prostate cancer.
-
more » « less
Summary Primary analysis of case–control studies focuses on the relationship between disease D and a set of covariates of interest (Y, X). A secondary application of the case–control study, which is often invoked in modern genetic epidemiologic association studies, is to investigate the interrelationship between the covariates themselves. The task is complicated owing to the case–control sampling, where the regression of Y on X is different from what it is in the population. Previous work has assumed a parametric distribution for Y given X and derived semiparametric efficient estimation and inference without any distributional assumptions about X. We take up the issue of estimation of a regression function when Y given X follows a homoscedastic regression model, but otherwise the distribution of Y is unspecified. The semiparametric efficient approaches can be used to construct semiparametric efficient estimates, but they suffer from a lack of robustness to the assumed model for Y given X. We take an entirely different approach. We show how to estimate the regression parameters consistently even if the assumed model for Y given X is incorrect, and thus the estimates are model robust. For this we make the assumption that the disease rate is known or well estimated. The assumption can be dropped when the disease is rare, which is typically so for most case–control studies, and the estimation algorithm simplifies. Simulations and empirical examples are used to illustrate the approach.
-
more » « less
Abstract Consider the setting where (i) individual‐level data are collected to build a regression model for the association between an event of interest and certain covariates, and (ii) some risk calculators predicting the risk of the event using less detailed covariates are available, possibly as algorithmic black boxes with little information available about how they were built. We propose a general empirical‐likelihood‐based framework to integrate the rich auxiliary information contained in the calculators into fitting the regression model, to make the estimation of regression parameters more efficient. Two methods are developed: one using working models to extract the calculator information and the other making a direct use of calculator predictions without working models. Theoretical and numerical investigations show that the calculator information can substantially reduce the variance of regression parameter estimation. As an application, we study the dependence of the risk of high‐grade prostate cancer on both conventional risk factors and newly identified molecular biomarkers by integrating information from the Prostate Biopsy Collaborative Group (PBCG) risk calculator, which was built based on conventional risk factors alone.
-
more » « less
Abstract There is a growing need for flexible general frameworks that integrate individual-level data with external summary information for improved statistical inference. External information relevant for a risk prediction model may come in multiple forms, through regression coefficient estimates or predicted values of the outcome variable. Different external models may use different sets of predictors and the algorithm they used to predict the outcome Y given these predictors may or may not be known. The underlying populations corresponding to each external model may be different from each other and from the internal study population. Motivated by a prostate cancer risk prediction problem where novel biomarkers are measured only in the internal study, this paper proposes an imputation-based methodology, where the goal is to fit a target regression model with all available predictors in the internal study while utilizing summary information from external models that may have used only a subset of the predictors. The method allows for heterogeneity of covariate effects across the external populations. The proposed approach generates synthetic outcome data in each external population, uses stacked multiple imputation to create a long dataset with complete covariate information. The final analysis of the stacked imputed data is conducted by weighted regression. This flexible and unified approach can improve statistical efficiency of the estimated coefficients in the internal study, improve predictions by utilizing even partial information available from models that use a subset of the full set of covariates used in the internal study, and provide statistical inference for the external population with potentially different covariate effects from the internal population.
