CERSI Collaborators: Joseph Ross, MD, MHS (Yale) (PI), Nilay Shah, PhD (formerly at Mayo Clinic) (PI), Juan Pablo Brito, MD (Mayo Clinic), Yihong Deng, PhD (Mayo Clinic), Kasia Lipska, MD (Yale)

FDA Collaborators: Nam Hee Choi, PhD, David Graham, MD, MPH, Myong-Jin Kim, PharmD, Rob Lionberger, PhD, Fairouz Makhlouf, PhD, Yandong Qiang, MS, PhD, MPH, Elena Rantou, PhD, Zhong Wang, PhD, Liang Zhao, PhD

CERSI In-Kind Collaborators: University of Wisconsin School of Medicine- James Hummel, MD (Now at Yale Univ.), University of California, San Francisco- Sanket Dhruva, MD, MHS

Project Start Date to End Date: May 2019 – February 2022 

Regulatory Science Challenge

Generic drugs are approved based on their chemical similarity, or bioequivalence, to the brand-name drug.  Patients and clinicians have raised concerns that switching between generic levothyroxine products made by different manufacturers may affect thyroid hormone levels.  Therefore, several endocrine organizations recommend that patients remain on the same dose preparation of generic drugs and avoid switching between different versions of L-thyroxine products.

Project Description and Findings

The goals of this project were to: 1) examine the rates of generic L-thyroxine preparation switching within one year of initiating L-thyroxine, and to examine factors associated with switching and 2) Compare thyrotropin stimulating hormone (TSH) levels among patients who switch vs. continue the same sourced levothyroxine product. To accomplish these goals, the CERSI used de-identified administrative claims data (information on doctors’ appointments, bills, insurance information, and other patient-provider communications) linked with laboratory results from a large database, OptumLabsTM Data Warehouse (OLDW), that includes information on privately insured and Medicare beneficiaries of all ages, as well as structured electronic health record data. Results showed that one in five patients switched generic drug manufactures, and switching was more likely to occur when multiple pharmacies were used to fill their prescription within one year of beginning treatment.  Additionally, despite switching between generic drug manufacturers for L-thyroxine products, the team found that switching products was not associated with clinically significant changes in thyrotropin values.

Publications

Brito JP, Deng Y, Ross JS, Choi NH, Graham DJ, Qiang Y, Rantou E, Wang Z, Zhao L, Shah ND, Lipska KJ. Association Between Generic-to-Generic Levothyroxine Switching and Thyrotropin Levels Among US Adults. JAMA Intern Med. 2022 Apr 1;182(4):418-425.

Brito JP, Deng Y, Ross JS, Choi NH, Graham DJ, Qiang Y, Rantou E, Wang Z, Zhao L, Shah ND, Lipska KJ. Rates of, and factors associated with, switching among generic levothyroxine preparations in commercially insured American adults. Endocrine. 2022 May;76(2):349-358.

Additional information can be found in here: CDER Spotlight