Medical reversal

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Medical reversal refers to when a newer and methodologically superior clinical trial produces results that contradict existing clinical practice and the older trials on which it is based. This leads to an intervention that was widely used falling out of favor, because new evidence either demonstrates that it is ineffective or that its harms exceed its benefits. It is distinct from replacement, which occurs when a newly developed medical treatment supersedes an older, less effective one as the standard of care.[1] Medical reversals are caused when a treatment is widely adopted even when there is not compelling evidence for its safety and effectiveness. For example, an intervention may be adopted because it "makes sense", or because there are observational studies supporting its putative benefits.[2] The negative effects of such reversals include harm to patients who received the intervention when it was considered relatively safe and effective, as well as reducing public trust in medicine.[3]

The term, medical reversal, was coined in 2011 by Vinay Prasad, Victor Gall and Adam Cifu in a research letter published in the Archives of Internal Medicine (now JAMA Internal Medicine).[3]

The term evidence reversal has also been proposed to refer to the same concept as medical reversal, but with a broader scope, including other scientific disciplines in addition to medical science.[4]

The tomato effect is a parallel concern. But, instead of clinical trials producing a different result, it is about changes in theory or the current understanding of a disease.[5][6]


A 2011 study of one year of original New England Journal of Medicine publications found that 13% of them constituted medical reversals.[3] A 2013 study of a decade of medical journal articles found that of the 363 articles focused on standard of care practices, 146, or about 40%, led to reversals of the practice.[7] A 2019 study of over 3,000 randomized controlled trials published in three prominent general medical journals concluded that 396 of these trials constituted medical reversals. The most common disease category among the reversals identified was cardiovascular disease.[8]


One example of medical reversal is diethylstilbestrol (DES). In the 1940s diethylstilbestrol was used to treat endometriosis until it was determined that it had the opposite effect and increased the risk of endometriosis in the treated women.[9][10]

In cases where this was given to pregnant women, DES was found to cause cancers in girls and women who had been exposed to this medication in utero when their mothers were pregnant The United States Food and Drug Administration subsequently withdrew approval of DES as a treatment for pregnant women.[11]

It was later determined that DES can also cause other major medical complications in those exposed.[11][12] In the exposed daughters of exposed women, those complications include not only the cancers previously discussed, but also an increased risk of miscarriage, premature birth, and endometriosis.[11][13][14]


  1. ^ Prasad V, Cifu A (December 2011). "Medical reversal: why we must raise the bar before adopting new technologies". Yale J Biol Med. 84 (4): 471–8. PMC 3238324. PMID 22180684.
  2. ^ Cifu AS, Prasad VK (December 2015). "Medical Debates and Medical Reversal". J Gen Intern Med. 30 (12): 1729–30. doi:10.1007/s11606-015-3481-5. PMC 4636561. PMID 26224155.
  3. ^ a b c Prasad, Vinay (2011-10-10). "The Frequency of Medical Reversal". Archives of Internal Medicine. 171 (18): 1675–6. doi:10.1001/archinternmed.2011.295. ISSN 0003-9926. PMID 21747003.
  4. ^ Sutton, Desirée; Qureshi, Riaz; Martin, Janet (February 2018). "Evidence reversal—when new evidence contradicts current claims: a systematic overview review of definitions and terms". Journal of Clinical Epidemiology. 94: 76–84. doi:10.1016/j.jclinepi.2017.10.004.
  5. ^ Goodwin JS, Goodwin JM (May 1984). "The tomato effect. Rejection of highly efficacious therapies". JAMA. 251 (18): 2387–90. doi:10.1001/jama.1984.03340420053025. PMID 6368890.
  6. ^ Hausenblas, Heather (18 August 2014). "Does Physical Activity Show Signs of a Tomato Effect?". US News & World Report. Retrieved 15 November 2014.
  7. ^ Prasad V, Vandross A, Toomey C, Cheung M, Rho J, Quinn S, Chacko SJ, Borkar D, Gall V, Selvaraj S, Ho N, Cifu A (August 2013). "A decade of reversal: an analysis of 146 contradicted medical practices". Mayo Clin Proc. 88 (8): 790–8. doi:10.1016/j.mayocp.2013.05.012. PMID 23871230.
  8. ^ Herrera-Perez, Diana; Haslam, Alyson; Crain, Tyler; Gill, Jennifer; Livingston, Catherine; Kaestner, Victoria; Hayes, Michael; Morgan, Dan; Cifu, Adam S (2019-06-11). Franco, Eduardo; Elshaug, Adam (eds.). "A comprehensive review of randomized clinical trials in three medical journals reveals 396 medical reversals". eLife. 8: e45183. doi:10.7554/eLife.45183. ISSN 2050-084X. PMC 6559784.
  9. ^ Karnaky KJ (December 1948). "The use of stilbestrol for endometriosis; preliminary report". South. Med. J. 41 (12): 1109–11. doi:10.1097/00007611-194812000-00013. PMID 18892822.
  10. ^ Barbieri RL (March 1998). "Endometriosis and the estrogen threshold theory. Relation to surgical and medical treatment". J Reprod Med. 43 (3 Suppl): 287–92. PMID 9564663.
  11. ^ a b c Veurink M, Koster M, Berg LT (June 2005). "The history of DES, lessons to be learned". Pharm World Sci. 27 (3): 139–43. doi:10.1007/s11096-005-3663-z. PMID 16096877.
  12. ^ "DES Update: For Consumers". United States Department of Health and Human Services: Centers for Disease Control and Prevention. Retrieved 2020-05-22.
  13. ^ Ottolina J, Schimberni M, Makieva S, Bartiromo L, Fazia T, Bernardinelli L, Viganò P, Candiani M, Gentilini D (August 2020). "Early-life factors, in-utero exposures and endometriosis risk: a meta-analysis". Reprod. Biomed. Online. 41 (2): 279–289. doi:10.1016/j.rbmo.2020.04.005. PMID 32532666.
  14. ^ Zondervan KT, Becker CM, Missmer SA (March 2020). "Endometriosis". N. Engl. J. Med. 382 (13): 1244–1256. doi:10.1056/NEJMra1810764. PMID 32212520.