Background Drug formularies, initially designed to promote the use of cost-effective generic drugs are now designed to maximize financial benefits for the pharmacy benefit management companies that negotiate drug purchase prices. In the largest publicly available formulary, 55% of mandated substitutions are not for generic versions of the same active ingredient and/or formulation and may not be medically or financially beneficial to patients.

Methods We modeled the effect of excluding novel agents for atrial fibrillation/venous thromboembolism, migraine prevention, and psoriasis, which all would require substitution with a different active ingredient. Using population data, market share of the two largest U.S. formularies, and 2021 prescription data, we calculated how many people could be affected by such exclusions. Using data from the published literature, we calculated how many of those individuals are likely to discontinue treatment and/or have adverse events due to a formulary exclusion.

Results The number of people likely to have adverse events due to the exclusion could be as high as one million for atrial fibrillation/venous thromboembolism, 900,000 for migraine prevention, and 500,000 for psoriasis. The numbers likely to discontinue treatment for their condition are as high as 924,000 for atrial fibrillation/venous thromboembolism, 646,000 for migraine, and 138,000 for psoriasis.

Conclusion Substitution with a nonequivalent treatment is common in formularies currently in use and is not without substantial consequences for hundreds of thousands of patients. Forced drug substitution results in costly increases in morbidity and mortality and should be part of the cost-benefit analysis of any formulary exclusion.

Robert Popovian is the founder of Conquest Advisors, LLC, owns stocks of biopharmaceutical companies, and was an employee of Pfizer for over two decades. He is a member of the Board of Councilors, University of Southern California, School of Pharmacy, Board of Directors, for University Pharmaco, LLC, Adjunct Clinical Faculty at Rutgers University, School of Pharmacy and serves as a consultant for the biopharmaceutical industry. The authors declare no other relevant conflicts of interest or financial relationships.

This study was funded by unrestricted educational grants from Amgen and Pfizer.

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COMPETING INTERESTS DISCLOSURE: Robert Popovian is the founder of Conquest Advisors, LLC, owns stocks of biopharmaceutical companies, and was an employee of Pfizer for over two decades. He is a member of the Board of Councilors, University of Southern California, School of Pharmacy, Board of Directors, for University Pharmaco, LLC, Adjunct Clinical Faculty at Rutgers University, School of Pharmacy and serves as a consultant for the biopharmaceutical industry. The authors declare no other relevant conflicts of interest or financial relationships.

FUNDING: This modeling study was funded by unrestricted educational grants from Amgen and Pfizer.

All data produced in the present study are available upon reasonable request to the authors