Practice of Epidemiology Adjusting for Covariates in Studies of Diagnostic, Screening, or Prognostic Markers: an Old Concept in a New Setting

The concept of covariate adjustment is well established in therapeutic and etiologic studies. However, it has received little attention in the growing area of medical research devoted to the development of markers for disease diagnosis, screening, or prognosis, where classification accuracy, rather than association, is of primary interest. In this paper, the authors demonstrate the need for covariate adjustment in studies of classification accuracy, discuss methods for adjusting for covariates, and distinguish covariate adjustment from several other related, but fundamentally different, uses for covariates. They draw analogies and contrasts throughout with studies of association.

[1]  M. Stampfer,et al.  A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer. , 1995, JAMA.

[2]  Lori E. Dodd,et al.  Partial AUC Estimation and Regression , 2003, Biometrics.

[3]  J. Oesterling,et al.  Influence of patient age on the serum PSA concentration. An important clinical observation. , 1993, The Urologic clinics of North America.

[4]  H. Morgenstern,et al.  Confounding in health research. , 2001, Annual review of public health.

[5]  Margaret S. Pepe,et al.  Biomarker Evaluation Using the Controls as a Reference Population , 2007 .

[6]  Gary Longton,et al.  Accommodating Covariates in Receiver Operating Characteristic Analysis , 2009 .

[7]  Margaret Sullivan Pepe,et al.  Standardizing Diagnostic Markers to Evaluate and Compare Their Performance , 2005, Epidemiology.

[8]  J. Pearl,et al.  Confounding and Collapsibility in Causal Inference , 1999 .

[9]  D. Dorfman,et al.  Maximum-likelihood estimation of parameters of signal-detection theory and determination of confidence intervals—Rating-method data , 1969 .

[10]  Margaret S. Pepe,et al.  Semiparametric Receiver Operating Characteristic Analysis to Evaluate Biomarkers for Disease , 2002 .

[11]  J A Hanley,et al.  The use of the 'binormal' model for parametric ROC analysis of quantitative diagnostic tests. , 1996, Statistics in medicine.

[12]  J. C. Ogilvie,et al.  Maximum-likelihood estimation of receiver operating characteristic curve parameters , 1968 .

[13]  M. Graffar.  [Modern epidemiology]. , 1971, Bruxelles medical.

[14]  J. Hanley.  The Robustness of the "Binormal" Assumptions Used in Fitting ROC Curves , 1988, Medical decision making : an international journal of the Society for Medical Decision Making.

[15]  Margaret Sullivan Pepe,et al.  The Analysis of Placement Values for Evaluating Discriminatory Measures , 2004, Biometrics.

[16]  J. Oesterling,et al.  The use of age-specific reference ranges for serum prostate specific antigen in men 60 years old or older. , 1995, The Journal of urology.

[17]  Holly Janes,et al.  Matching in Studies of Classification Accuracy: Implications for Analysis, Efficiency, and Assessment of Incremental Value , 2008, Biometrics.

[18]  Margaret Sullivan Pepe,et al.  Distribution-free ROC analysis using binary regression techniques. , 2002, Biostatistics.

[19]  John A. Swets,et al.  Evaluation of diagnostic systems : methods from signal detection theory , 1982 .

[20]  M. Pepe.  The Statistical Evaluation of Medical Tests for Classification and Prediction , 2003 .

[21]  Gary Longton,et al.  Accommodating Covariates in ROC Analysis. , 2009, The Stata journal.

[22]  Iris Pigeot,et al.  Handbook of epidemiology , 2005 .

[23]  J A Hanley,et al.  Sampling variability of nonparametric estimates of the areas under receiver operating characteristic curves: an update. , 1997, Academic radiology.

[24]  J. Swets.  Indices of discrimination or diagnostic accuracy: their ROCs and implied models. , 1986, Psychological bulletin.

[25]  Holly Janes,et al.  Adjusting for Covariate Effects on Classification Accuracy Using the Covariate-Adjusted ROC Curve , 2006 .

[26]  M. Pepe.  An Interpretation for the ROC Curve and Inference Using GLM Procedures , 2000, Biometrics.

[27]  Joseph E. Cavanaugh,et al.  Handbook of Epidemiology , 2006 .

[28]  Margaret Sullivan Pepe,et al.  Combining Several Screening Tests: Optimality of the Risk Score , 2002, Biometrics.

[29]  M. Pepe,et al.  Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker. , 2004, American journal of epidemiology.

[30]  Gary Longton,et al.  Estimation and Comparison of Receiver Operating Characteristic Curves , 2009, The Stata journal.