Abstract
There is almost unanimity that modern medicine should be “evidence based.” In this context, lack of prospectively randomized clinical trials (RCTs) is widely lamented in reproductive medicine. Some leading voices, indeed, increasingly suggest that only RCT-based clinical conclusions should be integrated into clinical practice, since lower levels of evidence are inadequate. We have argued that reproductive medicine requires special considerations because, like clinical oncology, fertility treatments (especially in older women) are time dependent. Unlike clinical oncology, reproductive medicine, however, does not receive substantial financial research support from government or industry and, at least in the United States, has, therefore, to be primarily funded via patient revenues. Given a 50% chance of receiving placebo, infertility patients are, understandably, reluctant to fund their own RCTs. We here selectively review this subject, contrasting opposing opinions recently published in the literature by a prominent reproductive scientist and one of the world’s leading experts on evidence-based medicine. Placing these recent publications into the evolving context of infertility practice, as also addressed in this journal in recent publications, we conclude that objective reasons explain why relatively few RCTs are performed in reproductive medicine and predict that this will not change in the foreseeable future. Reproductive medicine, therefore, has to find ways to develop satisfactory clinical evidence in other ways, satisfying patients’ rights to easy access to potentially beneficial medical treatments with low costs and low risks. The RCTs should be reserved for relatively high risk and/or high cost treatments.
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Gleicher N, Barad DH. Misplaced obsession with prospectively randomized studies. Reprod Biomed Online. 2010;21(4):440–443.
Evers JLH. A nod is as good as a wink to a blind horse. Hum Reprod. 2014;29(11):2355.
Greenhalgh T, Howick J, Maskrey N; For the Evidence Based Medicine Renaissance Group. Evidence based medicine: a movement in crisis? BMJ. 2014;348:g3725.
Siristatidis C, Vrachnis N, Vogiatzi P, et al. Potential pathophysiological mechanisms of the beneficial role of endometrial injury in in bitro fertilization outcome. Reprod Sci. 2014;21(8):955–965.
Zhang XH, Liu ZZ, Tang MX, Zhang YH, Hu L, Liao AH. Morphological changes and expression of cytokine after local endometrial injury in a mouse model [published online April 12, 2015]. Reprod Sci. 2015. doi:10.1177/1933719115580999.
Yeung TWY, Chai J, Li RHW, Lee VCY, Ho PC, Ng EHY. The effect of endometrial injury on ongoing pregnancy rate in unselected subfertile women undergoing in- vitro fertilization: a randomized controlled trial. Hum Reprod. 2014;29(11):2474–2481.
Barash A, Dekel N, Fieldust S, Segal I, Schechtman E, Granot I. Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization. Fertil Steril. 2003;79(6):1317–1322.
Boonstra H. Human embryo and fetal research: Medical support and political controversy. The Guttmacher Report on Public policy. 2001;4(1)1–4; Web site. http://www.guttmacher.Org/pubs/tgr/04/1/gr040103.html. Updated July 21, 2015.
Jayaprakasan K, Narkwichean A, Maalouf WE, Campbell BK. Efficacy of dehydroepiandrosterone to overcome the effect of ovarian ageing (DITTO): a proof of principle randomized controlled trial protocol. BMJ Open. 2014;4(10):e005767.
Gleicher N, Barad DH. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR). Reprod Biol Endocrinol. 2011;9:67.
Smith GCS, Pell P. Hazardous journey. Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomized controlled trials. BMJ. 2003;327(7429):1450–1461.
Imrie R, Ramey DW. The evidence for evidence-based medicine. Complement Ther Med. 2000;8(2):123–126.
Edzard E. How much of general practice is based on evidence? Br J Gen Pract. 2004;54(501):316.
Parmar MK, Barthel FM, Sydes M, et al. Speeding up the evaluation of new agents in cancer. J Natl Cancer Inst. 2008;100(17):1204–1214.
Lewis JR, Lipworth W, Kerridge I, Doran E. Dilemmas in the compassionate supply of investigational cancer drugs. Intern Med J. 2014;44(9):841–845.
Geffen N. Anything to stay alive: The challenge of a campaign for an experimental drug[published online May 15, 2015]. Dev World Bioeth. 2015. doi:10.1111/dewb.12084.
Caplan AL, Bateman-House A. Should patients in need be given access to experimental drugs? Expert Opin Pharmacother. 2015;16(9):1275–1279.
Shah SK, Wendler D, Danis M. Examining the ethics of clinical use of unproven interventions outside of clinical trials during the ebola epdemic. Am J Bioeth. 2015;15(4):11–16.
Caplan AL, Plunkett C, Levin B. Selecting the right tool for the job. Am J Bioeth. 2015;15(4):4–10.
Ethics Committee of the American Society for Reproductive Medicine. Fertility preservation and reproduction in patients facing gonadotoxic therapies: a committee opinion. Fertil Steril. 2013;100(5):1224–1231.
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Gleicher, N., Kushnir, V.A. & Barad, D.H. Why Prospectively Randomized Clinical Trials Have Been Rare in Reproductive Medicine and Will Remain So?. Reprod. Sci. 23, 6–10 (2016). https://doi.org/10.1177/1933719115597768
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DOI: https://doi.org/10.1177/1933719115597768