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Real world evidence in effectiveness, safety, and cost savings of generic levothyroxine: a systematic review

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Abstract

Purpose

Generic levothyroxine, approved through Abbreviated New Drug Application (ANDA), is available for generic substitution. But ANDA does not require nonclinical or clinical data to establish safety and efficacy. Post-marketing evidence in generic equivalence for marketed levothyroxine products is limited. We conducted a systematic review to synthesize evidence in effectiveness, safety, and cost savings between patients using generic and branded levothyroxine.

Methods

We systematically searched published literature from Medline, International Pharmaceutical Abstracts, APA PsycInfo, and CINAHL from inception through 04/18/2021. Included studies were limited to post-marketing empirical studies including patients who used levothyroxine products, with direct comparison between generic and brand levothyroxine, and published in English. Risk of bias was assessed using the National Institute of Health Study Quality Assessment Tools. Two reviewers independently extracted data and conducted quality assessment for included studies. Given that the nine studies are so diverse, a meta-analysis was not possible. Therefore we provided a narrative review of the included studies.

Results

Of 349 studies identified, nine met the inclusion criteria. Six studies compared thyrotropin levels and adverse events between generic and brand users and provided mixed findings. In addition, generic users may generate prescription cost savings for payers but had suboptimal medication adherence than brand users.

Conclusion

Findings from this systematic review highlighted the limited and mixed evidence in real-world clinical and economic outcomes for generic levothyroxine. Continuous post-marketing monitoring and assessment of generic drugs are warranted to ensure treatment effectiveness, patient safety, and achieve financial savings in prescription costs.

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Data availability

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References

  1. J.R. Garber, R.H. Cobin, H. Gharib, J.V. Hennessey, I. Klein, J.I. Mechanick, R. Pessah-Pollack, P.A. Singer, K.A. Woeber, American Association of Clinical Endocrinologists, and American Thyroid Association Taskforce On Hypothyroidism in Adults, Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid 22(12), 1200–1235 (2012)

    Article  CAS  Google Scholar 

  2. H.J. Baskin, R.H. Cobin, D.S. Duick, H. Gharib, R.B. Guttler, M.M. Kaplan, R.L. Segal, American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr. Pract.: Off. J. Am. College Endocrinol. Am. Assoc. Clin. Endocrinol. 8(6), 457–469 (2002)

    Article  Google Scholar 

  3. U.S. Food and Drug Administration. Abbreviated New Drug Application (ANDA). https://www.fda.gov/drugs/types-applications/abbreviated-new-drug-application-anda. Accessed 20 Jun 2021

  4. U.S. Food and Drug Administration. Generic drug facts. https://www.fda.gov/drugs/generic-drugs/generic-drug-facts. Accessed 20 Jun 2021

  5. M.J. Berg, R.A. Gross, L.S. Haskins, W.M. Zingaro, K.J. Tomaszewski, Generic substitution in the treatment of epilepsy: patient and physician perceptions. Epilepsy Behav. 13(4), 693–699 (2008)

    Article  Google Scholar 

  6. K. Sewell, S. Andreae, E. Luke, M.M. Safford, Perceptions of and barriers to use of generic medications in a rural African American population, Alabama, 2011. Prev. Chronic Dis. 9, E142 (2012)

    Article  Google Scholar 

  7. A.J. Keenum, J.E. Devoe, D.J. Chisolm, L.S. Wallace, Generic medications for you, but brand-name medications for me. Res. Soc. Adm. Pharm. 8(6), 574–578 (2012)

    Article  Google Scholar 

  8. W.H. Shrank, E.R. Cox, M.A. Fischer, J. Mehta, N.K. Choudhry, Patients’ perceptions of generic medications’. Health Aff 28(2), 546–556 (2009)

    Article  Google Scholar 

  9. T.A. Brennan, T.H. Lee, Allergic to generics. Ann. Intern. Med. 141(2), 126–130 (2004)

    Article  Google Scholar 

  10. A.J. O’Malley, R.G. Frank, A. Kaddis, B.M. Rothenberg, B.J. McNeil, Impact of alternative interventions on changes in generic dispensing rates. Health Serv. Res. 41(5), 1876–1894 (2006)

    Article  Google Scholar 

  11. J. Qian, A.U. Mishuk, R.A. Hansen, Does public perception bias lead to more frequent reporting of adverse events: branded vs generic drugs. Expert Opinion Drug Saf. 17(8), 753–756 (2018)

    Article  Google Scholar 

  12. American Thyroid Association. AACE, TES, and ATA joint position statement on the use and interchangeability of thyroxine products. (2004). https://www.thyroid.org/thyroxine-products-joint-position-statement/. Accessed 4 Feb 2020

  13. D. Moher, A. Liberati, J. Tetzlaff, D.G. Altman, Preferred Reporting Items for Systematic Reviews and Meta-analyses: the PRISMA statement. J. Clin. Epidemiol. 62(10), 1006–1012 (2009)

    Article  Google Scholar 

  14. U.S. Food and Drug Administration. Real-world data (RWD) and real-world evidence (RWE) are playing an increasing role in health care decisions. https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence. Accessed 20 Mar 2021

  15. National Heart, Lung, and Blood Institute. Study quality assessment tools. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools. Accessed 15 Aug 2020

  16. J.P. Brito, J.S. Ross, L. Sangaralingham, S.K. Dutcher, D.J. Graham, Z. Wang, Y. Wu, X. Yao, R.C. Smallridge, V. Bernet, N.D. Shah, K.J. Lipska, Comparative effectiveness of generic vs brand-name levothyroxine in achieving normal thyrotropin levels. JAMA Netw. Open 3(9), e2017645 (2020)

    Article  Google Scholar 

  17. M.A. Fischer, J. Avorn, Economic consequences of underuse of generic drugs: evidence from Medicaid and implications for prescription drug benefit plans. Health Serv. Res. 38(4), 1051–1063 (2003)

    Article  Google Scholar 

  18. J.V. Hennessey, A.O. Malabanan, B.R. Haugen, E.G. Levy, Adverse event reporting in patients treated with levothyroxine: results of the pharmacovigilance task force survey of the american thyroid association, american association of clinical endocrinologists, and the endocrine society. Endocr. Pract. 16(3), 357–370 (2010)

    Article  Google Scholar 

  19. Z. Hepp, K. Wyne, S.R. Manthena, S. Wang, V. Gossain, Adherence to thyroid hormone replacement therapy: a retrospective, claims database analysis. Current Med. Res. Opinion 34(9), 1673–1678 (2018)

    Article  Google Scholar 

  20. M. Katz, J. Scherger, S. Conard, L. Montejano, S. Chang, Healthcare costs associated with switching from brand to generic levothyroxine. Am. Health Drug Benefits 3(2), 127–134 (2010)

    PubMed  PubMed Central  Google Scholar 

  21. J.P. Lomenick, L. Wang, S.B. Ampah, B.R. Saville, F.I. Greenwald, Generic levothyroxine compared with synthroid in young children with congenital hypothyroidism. J. Clin. Endocrinol. Metab. 98(2), 653–658 (2013)

    Article  CAS  Google Scholar 

  22. J.M. Carswell, J.H. Gordon, E. Popovsky, A. Hale, R.S. Brown, Generic and brand-name L-thyroxine are not bioequivalent for children with severe congenital hypothyroidism. J. Clin. Endocrinol. Metab. 98(2), 610–617 (2013)

    Article  CAS  Google Scholar 

  23. B.J. Dong, W.W. Hauck, J.G. Gambertoglio, L. Gee, J.R. White, J.L. Bubp, F.S. Greenspan, Bioequivalence of generic and brand-name levothyroxine products in the treatment of hypothyroidism. JAMA 277(15), 1205–1213 (1997)

    Article  CAS  Google Scholar 

  24. R.C. Smallridge, L.R. Sangaralingham, R. Mwangi, F. Kusumoto, H. Van Houten, V. Bernet, Comparison of incident cardiovascular event rates between generic and brand l-thyroxine for the treatment of hypothyroidism. Mayo Clin. Proc. 94(7), 1190–1198 (2019)

    Article  CAS  Google Scholar 

  25. B.M. Davit, P.E. Nwakama, G.J. Buehler, D.P. Conner, S.H. Haidar, D.T. Patel, Y. Yang, L.X. Yu, J. Woodcock, Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration. Ann. Pharmacother. 43(10), 1583–1597 (2009)

    Article  CAS  Google Scholar 

  26. N. Huo, L. Chen, A. Ullah Mishuk, C. Li, R.A. Hansen, I. Harris, Z. Kiptanui, Z. Wang, S.K. Dutcher, J. Qian, Generic levothyroxine initiation and substitution among Medicare and Medicaid populations: a new user cohort study. Endocrine 68(2), 336–348 (2020)

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank Mrs Adelia Grabowsky, health sciences librarian of Auburn University, for her time and expertise in assisting in the development of search strategy used in this systematic review.

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  1. Auburn University Harrison School of Pharmacy, Auburn, AL, 36849, USA

    Jingjing Qian & Kaniz Afroz Tanni

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  1. Jingjing Qian
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Correspondence to Jingjing Qian.

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Qian, J., Tanni, K.A. Real world evidence in effectiveness, safety, and cost savings of generic levothyroxine: a systematic review. Endocrine 74, 228–234 (2021). https://doi.org/10.1007/s12020-021-02833-8

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