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Comparison of Standardization Methods for the Harmonization of Phenotype Data: An Application to Cognitive Measures.

ABSTRACT: Standardization procedures are commonly used to combine phenotype data that were measured using different instruments, but there is little information on how the choice of standardization method influences pooled estimates and heterogeneity. Heterogeneity is of key importance in meta-analyses of observational studies because it affects the statistical models used and the decision of whether or not it is appropriate to calculate a pooled estimate of effect. Using 2-stage individual participant data analyses, we compared 2 common methods of standardization, T-scores and category-centered scores, to create combinable memory scores using cross-sectional data from 3 Canadian population-based studies (the Canadian Study on Health and Aging (1991-1992), the Canadian Community Health Survey on Healthy Aging (2008-2009), and the Quebec Longitudinal Study on Nutrition and Aging (2004-2005)). A simulation was then conducted to assess the influence of varying the following items across population-based studies: 1) effect size, 2) distribution of confounders, and 3) the relationship between confounders and the outcome. We found that pooled estimates based on the unadjusted category-centered scores tended to be larger than those based on the T-scores, although the differences were negligible when adjusted scores were used, and that most individual participant data meta-analyses identified significant heterogeneity. The results of the simulation suggested that in terms of heterogeneity, the method of standardization played a smaller role than did different effect sizes across populations and differential confounding of the outcome measure across studies. Although there was general consistency between the 2 types of standardization methods, the simulations identified a number of sources of heterogeneity, some of which are not the usual sources considered by researchers.

SUBMITTER: Griffith LE

PROVIDER: S-EPMC5141949 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Biological subtypes in Alzheimer's disease, originally identified on neuropathological data, have been translated to in vivo biomarkers such as structural magnetic resonance imaging and positron emission tomography, to disentangle the heterogeneity within Alzheimer's disease. Although there is methodological variability across studies, comparable characteristics of subtypes are reported at the group level. In this study, we investigated whether group-level similarities translate to individual-level agreement across subtyping methods, in a head-to-head context. We compared five previously published subtyping methods. Firstly, we validated the subtyping methods in 89 amyloid-beta positive Alzheimer's disease dementia patients (reference group: 70 amyloid-beta negative healthy individuals) using structural magnetic resonance imaging. Secondly, we extended and applied the subtyping methods to 53 amyloid-beta positive prodromal Alzheimer's disease and 30 amyloid-beta positive Alzheimer's disease dementia patients (reference group: 200 amyloid-beta negative healthy individuals) using structural magnetic resonance imaging and tau positron emission tomography. Subtyping methods were implemented as outlined in each original study. Group-level and individual-level comparisons across methods were performed. Each individual subtyping method was replicated, and the proof-of-concept was established. At the group level, all methods captured subtypes with similar patterns of demographic and clinical characteristics, and with similar cortical thinning and tau positron emission tomography uptake patterns. However, at the individual level, large disagreements were found in subtype assignments. Although characteristics of subtypes are comparable at the group level, there is a large disagreement at the individual level across subtyping methods. Therefore, there is an urgent need for consensus and harmonization across subtyping methods. We call for the establishment of an open benchmarking framework to overcome this problem.

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Comparison of Standardization Methods for the Harmonization of Phenotype Data: An Application to Cognitive Measures.

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