Prescribing cascades in ambulatory care: A structured synthesis of evidence

Abstract

ImportanceThe strength of evidence for specific ambulatory care prescribing cascades, in which a marker drug is used to treat an adverse event caused by an index drug, has not been well characterized.ObjectiveTo perform a structured, systematic, and transparent review of the l evidence supporting ambulatory care prescribing cascadesDesign, setting, and participantsNinety‐four potential prescribing cascades identified through a previously published systematic review. Systematic search of the literature to further characterise prescribing cascades.Main outcome(1) Grading of evidence based on observational studies investigating associations between index and marker drugs, including: Level I ‐ strong evidence [i.e. multiple high‐quality studies]; Level II ‐ moderate evidence [i.e. single high‐quality study]; Level III ‐ fair evidence [no high‐quality studies but one or more moderate‐quality studies]; and Level IV ‐ poor evidence [other]. (2) Listing of the adverse event associated with the index drug in the product's United States Food and Drug Administration (FDA) label. (3) Synthesis of the evidence supporting mechanisms linking index drugs and associated adverse events.ResultsOf 99 potential cascades, 94 were supported by one or more confirmatory observational studies and were therefore included in this review. The 94 cascades related to 30 types of adverse drug reactions affecting 10 different anatomic/physiologic systems and were investigated by a total of 88 confirmatory studies, including prescription sequential symmetry analysis (n=51), cohort (n=30), and case‐control (n=7) studies. Overall, the evidence from observational studies was strong for 18 (19.1%) prescribing cascades, moderate for 61 (64.9%), fair for 13 (13.8%), and poor for 2 (2.1%). Although the evidence supporting mechanisms that link index drugs and associated adverse events was variable, FDA labels included information about the adverse event associated with the index drug for most (n=86) but not all of the 94 prescribing cascades.ConclusionsAlthough we identified 18 of 94 prescribing cascades supported by strong clinical evidence and most adverse events associated with index drugs are included in FDA label, the evidentiary basis for prescribing cascades varies, with many requiring further evidence of clinical relevance.

Stakeholder perceptions of and attitudes towards problematic polypharmacy and prescribing cascades: a qualitative study

“…Research to date has sought to identify lists of potential prescribing cascades [ 15–17 ]. More recent research has systematically assessed the evidence supporting these potential prescribing cascades [ 30 ]. Findings from these studies need to be translated into educational initiatives to raise awareness of potential prescribing cascades.…”