The weighted cumulative exposure method and its application to pharmacoepidemiology: A narrative review.

Publisher: Wiley Country of Publication: England NLM ID: 9208369 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1099-1557 (Electronic) Linking ISSN: 10538569 NLM ISO Abbreviation: Pharmacoepidemiol Drug Saf Subsets: MEDLINE

Original Publication: Chichester, West Sussex : Wiley, 1992-

Cohort Studies*; Humans ; Proportional Hazards Models ; Logistic Models ; Case-Control Studies

Purpose: The weighted cumulative exposure (WCE) method has been used in a number of fields including pharmacoepidemiology where it can account for intensity, duration and timing of exposures on the risk of an outcome. The method uses a data driven approach with flexible cubic B-splines to assign weights to past doses and select an aetiologically appropriate time window. Predictions of risk are possible for common exposure patterns encountered in real-world studies. The purpose of this study was to describe applications of the WCE method to pharmacoepidemiology and assess the strengths and limitations of the method.
Method: A literature search was undertaken to find studies applying the WCE method to the study of medicines. Articles published in PubMed using the search term 'weighted cumulative exposure' and articles citing Sylvestre et al. (2009) in Google Scholar or Scopus up to March 2023 were subsequently reviewed. Articles were selected based on title and review of abstracts.
Results: Seventeen clinical applications using the data-driven WCE method with flexible cubic splines were identified in the review. These included 3 case-control studies and 14 cohort studies, of which 12 were analysed with Cox proportional hazards models and 2 with logistic regression. Thirteen studies used time windows of 1 year or longer. Of 11 studies which compared conventional models with the WCE method, 10 (91%) studies found a better fit with WCE models while one had an equivalent fit. The freely available 'WCE' software package has facilitated the applications of the WCE method with flexible cubic splines.
Conclusions: The WCE method allows additional insights into the effect of cumulative exposure on outcomes, including the timing and intensity (dose) of the exposure on the risk. The flexibility of the method is particularly well suited to studies with long-term exposures that vary over time or where the current risk of an event is affected by how far the exposure is in the past, which is difficult to model with conventional definitions of exposure. Interpretation of the results can be more complex than for conventional models and would be facilitated by a standardised reporting framework.
(© 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

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APP1040938 National Health and Medical Research Council; GNT1157506 National Health and Medical Research Council

Keywords: cumulative exposure; pharmacoepidemiology; time-varying exposure; weighted cumulative exposure

Date Created: 20230925 Date Completed: 20240122 Latest Revision: 20240514

20240514

PMC10952599

10.1002/pds.5701

37749615