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Modeling of Functional Assessment Questionnaire (FAQ) as continuous bounded data from the ADNI database

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Abstract

An assessment of abilities to function independently in daily life is an important clinical endpoint for all Alzheimer’s disease (AD) patients and caregivers. A mathematical model was developed to describe the natural history of change of the Functional Assessment Questionnaire (FAQ) from data obtained in normal elderly, mild cognitive impairment, and mild AD in the AD neuroimaging initiative (ADNI) study. FAQ is a bounded outcome (ranging from 0 to 30), with 0 scored as “no impairment” and 30 as “severely impaired”. Since many normal elderly patients had 0 scores and some AD patients had scores of 30 in the ADNI database, a censored approach for handling the boundary data was compared with a standard approach, which ignores the bounded nature of the data. Baseline severity, ApoE4 genotype, age, sex, and imaging biomarkers were tested as covariates. The censored approach greatly improved the predictability of the disease progression in FAQ scores. The basic method for handling boundary data used in this analysis is also applicable to handle boundary observations for numerous other endpoints.

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Acknowledgments

Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation.

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Authors and Affiliations

  1. Pfizer Inc, Primary Care Business Unit, 445 Eastern Point Road, Groton, CT, 06340, USA

    K. Ito & B. W. Corrigan

  2. Ann Arbor Pharmacometrics Group, 110 E Miller Garden Suite, Ann Arbor, MI, 48104, USA

    M. M. Hutmacher

Authors
  1. K. Ito
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  2. M. M. Hutmacher
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  3. B. W. Corrigan
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Correspondence to K. Ito.

Additional information

Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.ucla.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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Ito, K., Hutmacher, M.M. & Corrigan, B.W. Modeling of Functional Assessment Questionnaire (FAQ) as continuous bounded data from the ADNI database. J Pharmacokinet Pharmacodyn 39, 601–618 (2012). https://doi.org/10.1007/s10928-012-9271-3

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  • DOI: https://doi.org/10.1007/s10928-012-9271-3

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