CERSI Collaborators: Joseph Ross, MD, MHS (Yale) (PI), Nilay Shah, PhD (formerly at Mayo Clinic, now at Delta Airlines) (PI), Juan Pablo Brito, MD (Mayo Clinic), Kasia Lipska, MD (Yale), Stefanie Rhode (Yale), Lindsey Sangaralingham, MPH (Mayo Clinic), Xiaoxi Yao, PhD (Mayo Clinic)

FDA Collaborators: Sarah Dutcher, PhD, David Graham, MD, MPH, Rob Lionberger, PhD, Yandong Qiang, MS, PhD, MPH, MHS, Zhong Wang, PhD, Yute Wu, 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: June 2017- June 2021

Regulatory Science Challenge

A generic drug is chemically identical, or bioequivalent, to its counterpart brand-name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use. In comparison to their branded counterparts, generic drugs may differ in their appearance, such as pill color or shape, and they are typically sold at substantially discounted prices. There have been concerns among patients and clinicians that generic and brand-name drugs are not equivalent and have differing effects on thyroid hormone levels and associated outcomes.

Project Description and Findings

The Yale-Mayo Clinic 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, OptumLabs^TM Data Warehouse (OLDW), that includes information on privately insured and Medicare beneficiaries of all ages, as well as structured electronic health record data, to characterize how generic and brand-name L-thyroxine products are used by patients, and then compare the effectiveness and safety of generic and brand-name L-thyroxine among new users of the medications. Specifically, the project focused on short-term management and stability of thyroid hormone levels among patients on therapy, as well as their long-term cardiovascular risk and other metabolic outcomes. The CERSI found that brand-name thyroid hormone product use declined from 2007 to 2016 among three large, national insurer beneficiary populations. Although certain patient characteristics were associated with brand-name use, prescriber specialty was the strongest predictor. In addition, initiation of generic vs brand-name levothyroxine formulations was associated with similar rates of normal and stable thyrotropin levels. These results suggest that generic levothyroxine as initial therapy for mild thyroid dysfunction is as effective as brand-name levothyroxine. Lastly, the team found no significant differences in cardiovascular outcomes and rates of falls and fractures for patients who filled brand versus generic L-thyroxine.

Publications

Ross JS, Rohde S, Sangaralingham L, Brito JP, Choi L, Dutcher SK, Graham DJ, Jenkins MR, Lipska KJ, Mendoza M, Qiang Y, Wang Z, Wu Y, Yao X, Shah ND. Generic and brand-name thyroid hormone drug use among commercially insured and Medicare beneficiaries, 2007 through 2016. J Clini Endocrinol Metab. 2019; 104(6):2305-2314.

Brito JP, Ross JS, Sangaralingham L, Dutcher SK, Graham DJ, Wang Z, Wu Y, Yao X, Smallridge RC, Bernet V, Shah ND, Lipska KJ. Comparative Effectiveness of Generic vs Brand-Name Levothyroxine in Achieving Normal Thyrotropin Levels. JAMA Netw Open. 2020 Sep 1;3(9):e2017645. doi: 10.1001/jamanetworkopen.2020.17645. PMID: 32997127.

Brito JP, Ross JS, Deng Y, Sangaralingham L, Graham DJ, Qiang Y, Wang Z, Yao X, Zhao L, Smallridge RC, Bernet V, Shah ND, Lipska KJ. Cardiovascular outcomes and rates of fractures and falls among patients with brand-name versus generic L-thyroxine use. Endocrine. 2021 Dec;74(3):592-602.

Also see CDER Spotlight on FDA.gov