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Updated: Aug 22, 2026

Diagonal Method to Measure Synergy Among Any Number of Drugs
Published on: June 21, 2018
Three complementary definitions of polypharmacy: methods, application and comparison of findings in a large
Benjamin G Fincke1, Kerri Snyder, Colleen Cantillon
1Department of Veterans Affairs, Center for Health Quality, Outcomes and Economic Research (CHQOER), Bedford, MA 01730, USA. gfincke@comcast.net
Purpose:
To develop and compare three operational definitions of polypharmacy using a large prescription database.
Methods:
We defined Cumulative polypharmacy as all prescriptions filled during a 178 day window--which captured 95% of eventual refills as calculated from Kaplan-Meier and cumulative incidence curves. Continuous polypharmacy was all prescriptions filled in two such windows 6 months apart. Simultaneous polypharmacy was the number of prescriptions active on a particular day, as determined by fill dates and amount of medication given. We applied these definitions to the outpatient prescription files of New England veterans and compared the resulting estimates of polypharmacy using descriptive statistics.
Results:
118,013 patients received at least one prescription between January 1998 and July 1999. Cumulative polypharmacy averaged 3.54 (SD = 4.95) medications and continuous polypharmacy averaged 1.96 (SD = 3.23). Examination of simultaneous polypharmacy over 40 2-week intervals revealed an average of 2.63 (CI 2.61-2.65), a minimum of 1.09 (CI 1.08-1.10) and maximum of 4.94 (CI 4.92-4.96). One arbitrarily selected observation point had an average of 3.87 (SD = 3.17).
Conclusions:
Our definitions of cumulative and continuous polypharmacy serve to set upper and lower bounds for the estimate of polypharmacy. Our method for simultaneous polypharmacy gives numbers that diverge in some respects, but it is better at showing transient changes in medications. The methods are complementary and allow exploration of various aspects of medication use, such as cumulative medication exposure over time, the influence of chronic medical problems, and the causes of rapid changes in medications.
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