Editing Randomized controlled trial (section)

== Ethics ==
Although the principle of [[clinical equipoise]] ("genuine uncertainty within the expert medical community... about the preferred treatment") common to clinical trials<ref name="Freedman-1987">{{Cite journal |vauthors=Freedman B |date=July 1987 |title=Equipoise and the ethics of clinical research |journal=The New England Journal of Medicine |volume=317 |issue=3 |pages=141–145 |doi=10.1056/NEJM198707163170304 |pmid=3600702}}</ref> has been applied to RCTs, the [[ethics]] of RCTs have special considerations.  For one, it has been argued that equipoise itself is insufficient to justify RCTs.<ref name="Gifford-1995">{{Cite journal |vauthors=Gifford F |date=April 1995 |title=Community-equipoise and the ethics of randomized clinical trials |journal=Bioethics |volume=9 |issue=2 |pages=127–148 |doi=10.1111/j.1467-8519.1995.tb00306.x |pmid=11653056}}</ref>  For another, "collective equipoise" can conflict with a lack of personal equipoise (e.g., a personal belief that an intervention is effective).<ref name="Edwards-1998">{{Cite journal |vauthors=Edwards SJ, Lilford RJ, Hewison J |date=October 1998 |title=The ethics of randomised controlled trials from the perspectives of patients, the public, and healthcare professionals |journal=BMJ |volume=317 |issue=7167 |pages=1209–1212 |doi=10.1136/bmj.317.7167.1209 |pmc=1114158 |pmid=9794861}}</ref>  Finally, [[Zelen's design]], which has been used for some RCTs, randomizes subjects ''before'' they provide informed consent, which may be ethical for RCTs of [[Screening (medicine)|screening]] and selected therapies, but is likely unethical "for most therapeutic trials."<ref name="Zelen-1979">{{Cite journal |vauthors=Zelen M |date=May 1979 |title=A new design for randomized clinical trials |journal=The New England Journal of Medicine |volume=300 |issue=22 |pages=1242–1245 |doi=10.1056/NEJM197905313002203 |pmid=431682}}</ref><ref name="Torgerson-1998">{{Cite journal |vauthors=Torgerson DJ, Roland M |date=February 1998 |title=What is Zelen's design? |journal=BMJ |volume=316 |issue=7131 |page=606 |doi=10.1136/bmj.316.7131.606 |pmc=1112637 |pmid=9518917}}</ref>

Although subjects almost always provide [[informed consent]] for their participation in an RCT, studies since 1982 have documented that RCT subjects may believe that they are certain to receive treatment that is best for them personally; that is, they do not understand the difference between research and treatment.<ref name="Appelbaum-1982">{{Cite journal |vauthors=Appelbaum PS, Roth LH, Lidz C |year=1982 |title=The therapeutic misconception: informed consent in psychiatric research |journal=International Journal of Law and Psychiatry |volume=5 |issue=3–4 |pages=319–329 |doi=10.1016/0160-2527(82)90026-7 |pmid=6135666}}</ref><ref name="Henderson-2007">{{Cite journal |vauthors=Henderson GE, Churchill LR, Davis AM, Easter MM, Grady C, Joffe S, Kass N, King NM, Lidz CW, Miller FG, Nelson DK, Peppercorn J, Rothschild BB, Sankar P, Wilfond BS, Zimmer CR |date=November 2007 |title=Clinical trials and medical care: defining the therapeutic misconception |journal=PLOS Medicine |volume=4 |issue=11 |pages=e324 |doi=10.1371/journal.pmed.0040324 |pmc=2082641 |pmid=18044980 |doi-access=free}}</ref> Further research is necessary to determine the prevalence of and ways to address this "[[therapeutic misconception]]".<ref name="Henderson-2007" />

The RCT method variations may also create cultural effects that have not been well understood.<ref name="Jain-2010">{{Cite journal |vauthors=Jain SL |year=2010 |title=The mortality effect: counting the dead in the cancer trial |url=https://pdfs.semanticscholar.org/aea1/45d2ff3b9c36b283cd9ca8cb61b839ef6993.pdf |journal=[[Public Culture]] |volume=21 |issue=1 |pages=89–117 |doi=10.1215/08992363-2009-017 |s2cid=143641293 |archive-url=https://web.archive.org/web/20200220002207/https://pdfs.semanticscholar.org/aea1/45d2ff3b9c36b283cd9ca8cb61b839ef6993.pdf |archive-date=2020-02-20}}</ref> For example, patients with terminal illness may join trials in the hope of being cured, even when treatments are unlikely to be successful.{{cn|date=March 2025}}

=== Trial registration ===
In 2004, the [http://www.icmje.org/ International Committee of Medical Journal Editors] (ICMJE) announced that all trials starting enrolment after July 1, 2005, must be registered prior to consideration for publication in one of the 12 member journals of the committee.<ref name="pmid15356289">{{Cite journal |vauthors=De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, Kotzin S, Laine C, Marusic A, Overbeke AJ, Schroeder TV, Sox HC, Van Der Weyden MB |date=September 2004 |title=Clinical trial registration: a statement from the International Committee of Medical Journal Editors |journal=The New England Journal of Medicine |volume=351 |issue=12 |pages=1250–1251 |doi=10.1056/NEJMe048225 |pmid=15356289 |doi-access=free}}</ref> However, trial registration may still occur late or not at all.<ref name="pmid22147862">{{Cite journal |vauthors=Law MR, Kawasumi Y, Morgan SG |date=December 2011 |title=Despite law, fewer than one in eight completed studies of drugs and biologics are reported on time on ClinicalTrials.gov |journal=Health Affairs |volume=30 |issue=12 |pages=2338–2345 |doi=10.1377/hlthaff.2011.0172 |pmid=22147862 |doi-access=free}}</ref><ref name="pmid19724045">{{Cite journal |vauthors=Mathieu S, Boutron I, Moher D, Altman DG, Ravaud P |date=September 2009 |title=Comparison of registered and published primary outcomes in randomized controlled trials |journal=JAMA |volume=302 |issue=9 |pages=977–984 |doi=10.1001/jama.2009.1242 |pmid=19724045 |doi-access=free}}</ref>
Medical journals have been slow in adapting policies requiring mandatory clinical trial registration as a prerequisite for publication.<ref>{{Cite journal |vauthors=Bhaumik S, Biswas T |date=March 2013 |title=Editorial policies of MEDLINE indexed Indian journals on clinical trial registration |journal=Indian Pediatrics |volume=50 |issue=3 |pages=339–340 |doi=10.1007/s13312-013-0092-2 |pmid=23680610 |s2cid=40317464}}</ref>