Abstract
Objective
A prescription cascade is a subsequent event that occurs when an adverse drug event
is misinterpreted as a new medical condition, resulting in the prescription of a potentially
unnecessary medication to treat this new condition. This study was designed to test
the hypothesis of whether prescribing cascades exist and their magnitude among older
individuals by using prescription sequence symmetry analysis (PSSA).
Design
A retrospective population-based cohort study based on data from Taiwan's National
Health Insurance Research Database (NHIRD), a nationwide claims-based database that
covers 99% of the population in Taiwan.
Setting and Participants
Patients receiving newly initiated index and marker drugs in the outpatient setting
between 2014 and 2016 were included. Those who received index and marker drugs on
the same date were excluded.
Measures
PSSA measures the propensity for a marker drug (eg, thyroxine) to be prescribed after
an index drug (eg, amiodarone) has been initiated, where the index drug is suspected
of inducing a side effect (eg, hypothyroidism) and the marker drug is used to treat
the side effect. We evaluated 14 PSSA sets as potential prescription cascade–related
drug pairs (index and marker drug), including 2 confirmatory analyses (eg, amiodarone
and thyroxin), to check the validity of the PSSA results and 12 exploratory analyses
of cardiovascular medication–related prescribing cascades (eg, statins and antidepressants).
The observation periods for sequences of incident marker drug use were 1 year before
and 1 year after the use of the incident index drug, and the symmetry of prescriptions
filled for the 2 periods was examined. The results of the PSSA were performed as the
crude sequence ratio (SR), defined as the ratio of patients initiating the marker
drug after the index drug (causal group) to those initiating the marker drug before
the index drug (noncausal group), and the adjusted SR (aSR) with 95% confidence intervals
(CIs).
Results
Among 12 potential prescription cascade–related drug pairs in exploratory analysis,
9 of them reached statistical significance, and aSR ranged from 1.02 to 1.46. Dihydropyridine
calcium channel blocker–induced edema showed the highest aSR (1.46, 95% CI 1.45–1.48),
and statin-induced muscle pain showed the lowest aSR (1.02, 95% CI 1.02–1.03).
Conclusions and Implications
Our study supported the application of PSSA in detecting prescribing cascades using
a nationwide claims database. Nevertheless, most previously reported prescribing cascades
among cardiovascular medications were shown to have a low effect size of sequence
ratios among older individuals.
Keywords
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Article info
Publication history
Published online: July 26, 2021
Footnotes
Y.C. and S.-T.H. contributed equally.
S.-T.H., F.Y.H., and L.K.C. received research assistantships from research projects (MOST 109–2634-F-010–001, MOST 110–2634-F-010–001) sponsored by the Ministry of Science and Technology Taiwan.
The authors declare no conflicts of interest.
Author Contributions: All authors meet the criteria for authorship stated in the Uniform Requirements for Manuscripts Submitted to Biomedical Journals. All authors drafted the article, revised it critically for important intellectual content, and approved the final version to be published. S.-T.H., T.C.H., F.Y.H., and L.K.C. designed the research. Y.C., S.-T.H., F.Y.H., and L.K.C. wrote the paper. Y.C. and T.C.H. performed the literature search. S.-T.H. analyzed data. F.Y.H. and L.K.C. provided critical methodological inputs. S.-T.H. and F.Y.H. provided methodological and statistical inputs. L.N.P. and L.K.C. contributed to the clinical interpretation. F.Y.H. and L.K.C. are guarantors.
The identification numbers for all entries in the NHIRD were encrypted to protect the privacy of individual patients. The study protocol was approved by the Institutional Review Board of the National Taiwan University Hospital (No. 201803134RINC).
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