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Original Article| Volume 154, P65-74, February 2023

Imputing missing laboratory results may return erroneous values because they are not missing at random

  • Carl van Walraven
    Correspondence
    Corresponding author. Ottawa Hospital Research Institute, ASB1-003, 1053 Carling Ave, Ottawa, ON K1Y 4E9, USA. Tel.: +1 613 761 4903; fax: +1 613 761 5492.
    Affiliations
    Professor of Medicine and Epidemiology & Community Medicine, University of Ottawa, Ontario, Canada

    Senior Scientist, Ottawa Hospital Research Institute, Ontario, Canada

    Senior Scientist, ICES, Ontario, Canada

    Department of Medicine, University of Ottawa, Ontario, Canada

    Department of Epidemiology & Community Medicine, University of Ottawa, Ottawa Hospital Research Institute, ICES (formerly Institute for Clinical Evaluative Sciences), Ontario, Canada
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  • Christopher McCudden
    Affiliations
    Associate Professor, Department of Pathology & Lab. Medicine, University of Ottawa, Ontario, Canada

    Clinical Biochemist, Division of Biochemistry, The Ottawa Hospital, Ontario, Canada
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  • Peter C. Austin
    Affiliations
    Senior Scientist, ICES, Ontario, Canada

    Professor, Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Canada
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Published:December 14, 2022DOI:https://doi.org/10.1016/j.jclinepi.2022.12.011

      Abstract

      Background and Objectives

      Regression models incorporating laboratory tests treat unordered tests as missing and are often imputed. Imputation typically assumes that data are “missing at random” (MAR, test's order status is unrelated to its result after accounting for other variables). This study examined the validity of this assumption.

      Methods

      We included 14 biochemistry tests. All tests were measured regardless of test order status. Test-stratified multiple linear regression determined the independent association between test result and order status after adjusting for patient age, sex, comorbidities, and patient location. Testing likelihood models were created for all tests using hospital-wide data.

      Results

      Four hundred thirty-four patients were included (mean age [standard deviation] 60.7 [19.1], 50.5% female). In 9 of 14 tests (64.2%), test results were significantly associated with order status after adjustment. Results were significantly more abnormal when tests were ordered for 6 tests and significantly more normal for 3 tests. Test abnormality increased as testing likelihood decreased.

      Conclusions

      These data suggest that laboratory data are often not MAR. The direction and extent of differences in missing laboratory test values varies between tests. Overall the abnormality of ordered tests increased as testing likelihood decreased. These results suggest that imputating missing laboratory data may return biased values.

      Keywords

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