A global sensitivity analysis of performance of a medical diagnostic test when verification bias is present.

Current advances in technology provide less invasive or less expensive diagnostic tests for identifying disease status. When a diagnostic test is evaluated against an invasive or expensive gold standard test, one often finds that not all patients undergo the gold standard test. The sensitivity and specificity estimates based only on the patients with verified disease are often biased.

Evaluating medical diagnostic tests at the subunit level in the presence of verification bias.

We advocate that medical diagnostic tests should be evaluated at the subunit level instead of the patient level if a disease can occur in multiple parts/units within a patient, for example, vessels, segments, ears, eyes etc. When a non-invasive test is compared to an invasive gold standard test, often not all of the subunits receive the gold standard test and verification bias is present if the subunits without the gold standard test are discarded. Here we address estimation and inference issues in assessing the performance of medical diagnostic tests at the subunit level while accounting for verification bias and the correlation among subunits.

Accounting for nonignorable verification bias in assessment of diagnostic tests.

A "gold" standard test, providing definitive verification of disease status, may be quite invasive or expensive. Current technological advances provide less invasive, or less expensive, diagnostic tests. Ideally, a diagnostic test is evaluated by comparing it with a definitive gold standard test.

Missing data in the 2 x 2 table: patterns and likelihood-based analysis for cross-sectional studies with supplemental sampling.

Standard measures of crude association in the context of a cross-sectional study are the risk difference, relative risk and odds ratio as derived from a 2x 2 table. Most such studies are subject to missing data on disease, exposure, or both, introducing bias into the usual complete-case analysis. We describe several scenarios distinguished by the manner in which missing data arise, and for each we adjust the natural multinomial likelihood to properly account for missing data.

A note on estimating crude odds ratios in case-control studies with differentially misclassified exposure.

Morrissey and Spiegelman (1999, Biometrics 55, 338 344) provided a comparative study of adjustment methods for exposure misclassification in case-control studies equipped with an internal validation sample. In addition to the maximum likelihood (ML) approach, they considered two intuitive procedures based on proposals in the literature. Despite appealing ease of computation associated with the latter two methods, efficiency calculations suggested that ML was often to be recommended for the analyst with access to a numerical routine to facilitate it.

Overall concordance correlation coefficient for evaluating agreement among multiple observers.

Accurate and precise measurement is an important component of any proper study design. As elaborated by Lin (1989, Biometrics 45, 255-268), the concordance correlation coefficient (CCC) is more appropriate than other indices for measuring agreement when the variable of interest is continuous. However, this agreement index is defined in the context of comparing two fixed observers.

Weighted least-squares approach for comparing correlated kappa.

In the medical sciences, studies are often designed to assess the agreement between different raters or different instruments. The kappa coefficient is a popular index of agreement for binary and categorical ratings. Here we focus on testing for the equality of two dependent kappa coefficients.

Correlating two viral load assays with known detection limits.

A timely objective common to many HIV studies involves assessing the correlation between two different measures of viral load obtained from each of a sample of patients. This correlation has scientific utility in a number of contexts, including those aimed at a comparison of competing assays for quantifying virus and those aimed at determining the level of association between viral loads in two different reservoirs using the same assay. A complication for the analyst seeking valid point and interval estimates of such a correlation is the fact that both variables may be subject to left censoring due to values below assay detection limits.

Modeling concordance correlation via GEE to evaluate reproducibility.

Clinical studies are often concerned with assessing whether different raters/methods produce similar values for measuring a quantitative variable. Use of the concordance correlation coefficient as a measure of reproducibility has gained popularity in practice since its introduction by Lin (1989, Biometrics 45, 255-268). Lin's method is applicable for studies evaluating two raters/two methods without replications.

Efficiency of estimating vaccine efficacy for susceptibility and infectiousness: randomization by individual versus household.

In designing vaccine efficacy studies based on the secondary attack rate (SAR) or transmission probability in which both vaccine efficacy for susceptibility, VE(S), and vaccine efficacy for infectiousness, VE(I), are estimated, the allocation of vaccine and placebo within transmission units has an important influence on the efficiency of the study. We compared the following randomization schemes that result in different allocations of vaccine and placebo within two-member households: (1) randomization by individual for a mixed allocation, (2) randomization by transmission unit for concordant allocation, and (3) randomization of only one individual in each transmission unit to either vaccine or placebo. There is a complex interaction among the VE(S), VE(I), and the SAR that determines which allocation of vaccine and placebo within households provides the most information.

Early nutrition and later adiposity.

The objective was to review whether nutrition during pregnancy and the first 3 y of life predisposes individuals to be fatter as adults. The roles of undernutrition, overnutrition and breastfeeding were considered. The evidence that poor nutrition in early life is a risk factor for increased fatness later in life is inconclusive.

Overweight and obesity in preschool children from developing countries.

Objectives: To estimate levels and trends in overweight and obesity in preschool children from developing countries; to study how overweight varies by the educational level of the mother, by urban or rural residence, and by gender; to investigate how these relationships are related to the gross national product (GNP).

Design: 71 national nutrition surveys since 1986 from 50 countries were used.

Subjects: 150,482 children 12 to 60 months from the most recent survey from each country were the primary sample.

Sample size estimation for survival outcomes in cluster-randomized studies with small cluster sizes.

We present a method for computing sample size for cluster-randomized studies involving a large number of clusters with relatively small numbers of observations within each cluster. For multivariate survival data, only the marginal bivariate distribution is assumed to be known. The validity of this assumption is also discussed.

Obesity in women from developing countries.

Objectives: The key objective was to estimate obesity (>/=30 kg/m2) in women 15-49 y from developing countries. A second objective was to study how obesity varies by educational level and by residence in urban and rural areas. A third objective was to investigate how national incomes shape the relationship between obesity and eduction or residence.

Role of intergenerational effects on linear growth.

Current knowledge on the role of intergenerational effects on linear growth is reviewed on the basis of a literature search and recent findings from an ongoing study in Guatemala. Fourteen studies were identified, most of which examined the intergenerational relationships in birth weight. Overall, for every 100 g increase in maternal birth weight, her child's birth weight increased by 10-20 g.

Obesity in Latin American women and children.

National surveys conducted since 1982 were used to assess maternal and child obesity in Latin American and Caribbean countries and in U. S. residents of Mexican descent.

Early childhood determinants of age at menarche in rural guatemala.

The influence of early childhood determinants on age at menarche was investigated in a sample of Guatemalan women who participated as children in a nutrition intervention study conducted from 1969 to 1977. Age at menarche was retrospectively estimated in 1991 and 1992. Mean age at menarche was 13.