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]

Contents

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]

Prevalence

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]

Diethylstilbestrol

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]

Related Research Articles

Evidence-based medicine (EBM) is "the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients." The aim of EBM is to integrate the experience of the clinician, the values of the patient, and the best available scientific information to guide decision-making about clinical management. The term was originally used to describe an approach to teaching the practice of medicine and improving decisions by individual physicians about individual patients.

<span class="mw-page-title-main">Randomized controlled trial</span> Form of scientific experiment

A randomized controlled trial is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical techniques, medical devices, diagnostic procedures or other medical treatments.

<span class="mw-page-title-main">Diethylstilbestrol</span> Chemical compound

Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication, which is presently rarely used. In the past, it was widely used for a variety of indications, including pregnancy support for those with a history of recurrent miscarriage, hormone therapy for menopausal symptoms and estrogen deficiency, treatment of prostate cancer and breast cancer, and other uses. By 2007, it was only used in the treatment of prostate cancer and breast cancer. In 2011, Hoover and colleagues reported on adverse health outcomes linked to DES including infertility, miscarriage, ectopic pregnancy, preeclampsia, preterm birth, stillbirth, infant death, menopause prior to age 45, breast cancer, cervical cancer, and vaginal cancer. While most commonly taken by mouth, DES was available for use by other routes as well, for instance, vaginal, topical, and by injection.

Orthomolecular medicine is a form of alternative medicine that aims to maintain human health through nutritional supplementation. The concept builds on the idea of an optimal nutritional environment in the body and suggests that diseases reflect deficiencies in this environment. Treatment for disease, according to this view, involves attempts to correct "imbalances or deficiencies based on individual biochemistry" by use of substances such as vitamins, minerals, amino acids, trace elements and fatty acids. The notions behind orthomolecular medicine are not supported by sound medical evidence, and the therapy is not effective for chronic disease prevention; even the validity of calling the orthomolecular approach a form of medicine has been questioned since the 1970s.

Megavitamin therapy is the use of large doses of vitamins, often many times greater than the recommended dietary allowance (RDA) in the attempt to prevent or treat diseases. Megavitamin therapy is typically used in alternative medicine by practitioners who call their approach orthomolecular medicine. Vitamins are useful in preventing and treating illnesses specifically associated with dietary vitamin shortfalls, but the conclusions of medical research are that the broad claims of disease treatment by advocates of megavitamin therapy are unsubstantiated by the available evidence. It is generally accepted that doses of any vitamin greatly in excess of nutritional requirements will result either in toxicity or in the excess simply being metabolised; thus evidence in favour of vitamin supplementation supports only doses in the normal range. Critics have described some aspects of orthomolecular medicine as food faddism or even quackery. Research on nutrient supplementation in general suggests that some nutritional supplements might be beneficial, and that others might be harmful; several specific nutritional therapies are associated with an increased likelihood of the condition they are meant to prevent.

A hierarchy of evidence, comprising levels of evidence (LOEs), that is, evidence levels (ELs), is a heuristic used to rank the relative strength of results obtained from experimental research, especially medical research. There is broad agreement on the relative strength of large-scale, epidemiological studies. More than 80 different hierarchies have been proposed for assessing medical evidence. The design of the study and the endpoints measured affect the strength of the evidence. In clinical research, the best evidence for treatment efficacy is mainly from meta-analyses of randomized controlled trials (RCTs). Systematic reviews of completed, high-quality randomized controlled trials – such as those published by the Cochrane Collaboration – rank the same as systematic review of completed high-quality observational studies in regard to the study of side effects. Evidence hierarchies are often applied in evidence-based practices and are integral to evidence-based medicine (EBM).

David Lawrence Sackett was an American-Canadian physician and a pioneer in evidence-based medicine. He is known as one of the fathers of Evidence-Based Medicine. He founded the first department of clinical epidemiology in Canada at McMaster University, and the Oxford Centre for Evidence-Based Medicine. He is well known for his textbooks Clinical Epidemiology and Evidence-Based Medicine.

Vaginal cancer is an extraordinarily rare form of cancer that develops in the tissue of the vagina. Primary vaginal cancer originates from the vaginal tissue – most frequently squamous cell carcinoma, but primary vaginal adenocarcinoma, sarcoma, and melanoma have also been reported – while secondary vaginal cancer involves the metastasis of a cancer that originated in a different part of the body. Secondary vaginal cancer is more common. Signs of vaginal cancer may include abnormal vaginal bleeding, dysuria, tenesmus, or pelvic pain, though as many as 20% of women diagnosed with vaginal cancer are asymptomatic at the time of diagnosis. Vaginal cancer occurs more frequently in women over age 50, and the mean age of diagnosis of vaginal cancer is 60 years. It often can be cured if found and treated in early stages. Surgery alone or surgery combined with pelvic radiation is typically used to treat vaginal cancer.

A clinical prediction rule or clinical probability assessment specifies how to use medical signs, symptoms, and other findings to estimate the probability of a specific disease or clinical outcome.

Clear-cell adenocarcinoma of the vagina is a rare adenocarcinoma often linked to prenatal exposure to diethylstilbestrol (DES), a drug which was prescribed in high-risk pregnancy.

Female genital disease is a disorder of the structure or function of the female reproductive system that has a known cause and a distinctive group of symptoms, signs, or anatomical changes. The female reproductive system consists of the ovaries, fallopian tubes, uterus, vagina, and vulva. Female genital diseases can be classified by affected location or by type of disease, such as malformation, inflammation, or infection.

Neonatal withdrawal or neonatal abstinence syndrome (NAS) or neonatal opioid withdrawal syndrome (NOWS) is a withdrawal syndrome of infants after birth caused by in utero exposure to drugs of dependence, most commonly opioids. Common signs and symptoms include tremors, irritability, vomiting, diarrhea, and fever. NAS is primarily diagnosed with a detailed medication history and scoring systems. First-line treatment should begin with non-medication interventions to support neonate growth, though medication interventions may be used in certain situations.

Steven E. Nissen is an American cardiologist, researcher and patient advocate. He was chairman of cardiovascular medicine at the Cleveland Clinic, in Cleveland, Ohio.

The tomato effect occurs when effective therapies for a condition are rejected, usually because they do not make sense in the context of the current understanding or theory of the disease in question. The name refers to the fact that tomatoes were rejected as a food source by most North Americans until the end of the 19th century, because the prevailing belief at the time was that they were poisonous.

<span class="mw-page-title-main">T-shaped uterus</span> Medical condition

A t-shaped uterus is a type of uterine malformation wherein the uterus is shaped resembling the letter T. This is typically observed in DES-exposed women. It is recognised in the ESHRE/ESGE classification, and is associated with failed implantation, increased risk of ectopic pregnancy, miscarriage and preterm delivery. There is a surgical procedure to correct the malformation.

<span class="mw-page-title-main">High-dose estrogen therapy</span> Type of hormone therapy

High-dose estrogen therapy (HDE) is a type of hormone therapy in which high doses of estrogens are given. When given in combination with a high dose of progestogen, it has been referred to as pseudopregnancy. It is called this because the estrogen and progestogen levels achieved are in the range of the very high levels of these hormones that occur during pregnancy. HDE and pseudopregnancy have been used in medicine for a number of hormone-dependent indications, such as breast cancer, prostate cancer, and endometriosis, among others. Both natural or bioidentical estrogens and synthetic estrogens have been used and both oral and parenteral routes may be used.

Vinayak K. Prasad is an American hematologist-oncologist and health researcher. He is a professor of Epidemiology and Biostatistics at the University of California, San Francisco (UCSF). He is the author of the books Ending Medical Reversal (2015) and Malignant (2020).

Diethylstilbestrol (DES), a synthetic nonsteroidal estrogen which was previously used clinically to support pregnancy, has been linked to a variety of long-term adverse effects in women who were treated with it during pregnancy and in their offspring.

Adam Seth Cifu is an American physician, academic, author and researcher. He is a Professor of Medicine and Director of Academic Programming, Bucksbaum Institute for Clinical Excellence at the University of Chicago.

<i>Ending Medical Reversal</i> 2015 book by Vinay Prasad and Adam Cifu

Ending Medical Reversal: Improving Outcomes, Saving Lives is a nonfiction book written by Vinay Prasad and Adam Cifu, published in 2015 by Johns Hopkins University Press.

References

  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. 1 2 3 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. PMID   29045807.
  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?". U.S. 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 . PMID   31182188.
  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. S2CID   220549540.
  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. 1 2 3 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. S2CID   12630813.
  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. S2CID   214644045.
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