Dataset Information

Many Flavors of Model-Based Meta-Analysis: Part II - Modeling Summary Level Longitudinal Responses.

ABSTRACT: Meta-analyses typically assess comparative treatment response for an end point at specific timepoints across studies. However, during drug development, it is often of interest to understand the response time-course of competitor compounds for a variety of purposes. Examples of such application include informing study design and characterizing the onset, maintenance, and offset of action. This tutorial acts as a "points for consideration" document, reviews relevant literature, and fits a longitudinal model to an example dataset.

SUBMITTER: Boucher M

PROVIDER: S-EPMC5980518 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Many Flavors of Model-Based Meta-Analysis: Part II - Modeling Summary Level Longitudinal Responses.

Boucher Martin M Bennetts Meg M

CPT: pharmacometrics & systems pharmacology 20180420 5

Meta-analyses typically assess comparative treatment response for an end point at specific timepoints across studies. However, during drug development, it is often of interest to understand the response time-course of competitor compounds for a variety of purposes. Examples of such application include informing study design and characterizing the onset, maintenance, and offset of action. This tutorial acts as a "points for consideration" document, reviews relevant literature, and fits a longitud ...[more]

PMID: 29569841

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Project description:BackgroundGreater epidemiologic understanding of the relationships among fetal-infant mortality and its prognostic factors, including birthweight, could have vast public health implications. A key step toward that understanding is a realistic and tractable framework for analyzing birthweight distributions and fetal-infant mortality. The present paper is the second of a two-part series that introduces such a framework.MethodsWe propose estimating birthweight-specific mortality within each component of a normal mixture model representing a birthweight distribution, the number of components having been determined from the data rather than fixed a priori.ResultsWe address a number of methodological issues related to our proposal, including the construction of confidence intervals for mortality risk at any given birthweight within a component, for odds ratios comparing mortality within two different components from the same population, and for odds ratios comparing mortality within analogous components from two different populations. As an illustration we find that, for a population of white singleton infants, the odds of mortality at 3000 g are an estimated 4.15 times as large in component 2 of a 4-component normal mixture model as in component 4 (95% confidence interval, 2.04 to 8.43). We also outline an extension of our framework through which covariates could be probabilistically related to mixture components. This extension might allow the assertion of approximate correspondences between mixture components and identifiable subpopulations.ConclusionsThe framework developed in this paper does not require infants from compromised pregnancies to share a common birthweight-specific mortality curve, much less assume the existence of an interval of birthweights over which all infants have the same curve. Hence, the present framework can reveal heterogeneity in mortality that is undetectable via a contaminated normal model or a 2-component normal mixture model.

Dataset Information

Many Flavors of Model-Based Meta-Analysis: Part II - Modeling Summary Level Longitudinal Responses.

Publications

Many Flavors of Model-Based Meta-Analysis: Part II - Modeling Summary Level Longitudinal Responses.

Similar Datasets

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