Editing Randomized controlled trial (section)

== Advantages ==
RCTs are considered to be the most reliable form of [[scientific method|scientific evidence]] in the [[hierarchy of evidence]] that influences healthcare policy and practice because RCTs reduce spurious causality and bias. Results of RCTs may be combined in [[systematic review]]s which are increasingly being used in the conduct of [[evidence-based practice]]. Some examples of scientific organizations' considering RCTs or systematic reviews of RCTs to be the highest-quality evidence available are:
* As of 1998, the [[National Health and Medical Research Council]] of Australia designated "Level I" evidence as that "obtained from a [[systematic review]] of all relevant randomised controlled trials" and "Level II" evidence as that "obtained from at least one properly designed randomised controlled trial."<ref>{{Cite book |last=National Health and Medical Research Council |url=http://www.nhmrc.gov.au/_files_nhmrc/file/publications/synopses/cp30.pdf |title=A guide to the development, implementation and evaluation of clinical practice guidelines |date=1998-11-16 |publisher=Commonwealth of Australia |isbn=978-1-86496-048-8 |location=Canberra |page=56 |access-date=2010-03-28 |archive-url=https://web.archive.org/web/20171014045833/https://www.nhmrc.gov.au/_files_nhmrc/file/publications/synopses/cp30.pdf |archive-date=2017-10-14}}</ref>
* Since at least 2001, in making [[clinical practice guideline]] recommendations the [[United States Preventive Services Task Force]] has considered both a study's design and its [[internal validity]] as indicators of its quality.<ref name="Harris-2001">{{Cite journal |vauthors=Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, Atkins D |date=April 2001 |title=Current methods of the US Preventive Services Task Force: a review of the process |journal=American Journal of Preventive Medicine |volume=20 |issue=3 Suppl |pages=21–35 |doi=10.1016/S0749-3797(01)00261-6 |pmid=11306229 |collaboration=Methods Work Group; Third US Preventive Services Task Force}}</ref> It has recognized "evidence obtained from at least one properly randomized controlled trial" with good [[internal validity]] (i.e., a rating of "I-good") as the highest quality evidence available to it.<ref name="Harris-2001" />
* The [[Evidence-based medicine#Grade Working Group|GRADE Working Group]] concluded in 2008 that "randomised trials without important limitations constitute high quality evidence."<ref name="Guyatt-2008">{{Cite journal |vauthors=Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ |date=May 2008 |title=What is "quality of evidence" and why is it important to clinicians? |journal=BMJ |volume=336 |issue=7651 |pages=995–998 |doi=10.1136/bmj.39490.551019.BE |pmc=2364804 |pmid=18456631 |collaboration=GRADE Working Group}}</ref>
* For issues involving "Therapy/Prevention, Aetiology/Harm", the [[Oxford Centre for Evidence-based Medicine]] as of 2011 defined "Level 1a" evidence as a systematic review of RCTs that are consistent with each other, and "Level 1b" evidence as an "individual RCT (with narrow [[Confidence Interval]])."<ref>{{Cite web |last=Oxford Centre for Evidence-based Medicine |date=2011-09-16 |title=Levels of evidence |url=http://www.cebm.net/index.aspx?o=1025 |access-date=2012-02-15}}</ref>

Notable RCTs with unexpected results that contributed to changes in clinical practice include:
* After [[Food and Drug Administration]] approval, the [[antiarrhythmic agents]] [[flecainide]] and [[encainide]] came to market in 1986 and 1987 respectively.<ref name="Anderson-1997">{{Cite journal |vauthors=Anderson JL, Pratt CM, Waldo AL, Karagounis LA |date=January 1997 |title=Impact of the Food and Drug Administration approval of flecainide and encainide on coronary artery disease mortality: putting "Deadly Medicine" to the test |journal=The American Journal of Cardiology |volume=79 |issue=1 |pages=43–47 |doi=10.1016/S0002-9149(96)00673-X |pmid=9024734}}</ref> The non-randomized studies concerning the drugs were characterized as "glowing",<ref name="Rubin-2006">{{Cite news |date=2006-10-16 |title=In medicine, evidence can be confusing - deluged with studies, doctors try to sort out what works, what doesn't |url=https://www.usatoday.com/news/health/2006-10-15-medical-evidence-cover_x.htm |access-date=2010-03-22 |work=USA Today |vauthors=Rubin R}}</ref> and their sales increased to a combined total of approximately 165,000 prescriptions per month in early 1989.<ref name="Anderson-1997" />  In that year, however, a preliminary report of an RCT concluded that the two drugs increased mortality.<ref name="CAST-1989">{{Cite journal |last=Cardiac Arrhythmia Suppression Trial (CAST) Investigators |date=August 1989 |title=Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction |journal=The New England Journal of Medicine |volume=321 |issue=6 |pages=406–412 |doi=10.1056/NEJM198908103210629 |pmid=2473403}}</ref>  Sales of the drugs then decreased.<ref name="Anderson-1997" />
* Prior to 2002, based on observational studies, it was routine for physicians to prescribe hormone replacement therapy for post-menopausal women to prevent [[myocardial infarction]].<ref name="Rubin-2006" /> In 2002 and 2004, however, published RCTs from the [[Women's Health Initiative]] claimed that women taking hormone replacement therapy with estrogen plus progestin had a higher rate of myocardial infarctions than women on a placebo, and that estrogen-only hormone replacement therapy caused no reduction in the incidence of coronary heart disease.<ref name="Rossouw-2002" /><ref name="Anderson-2004">{{Cite journal |vauthors=Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O'Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S |date=April 2004 |title=Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial |journal=JAMA |volume=291 |issue=14 |pages=1701–1712 |doi=10.1001/jama.291.14.1701 |pmid=15082697 |doi-access=free}}</ref>  Possible explanations for the discrepancy between the observational studies and the RCTs involved differences in methodology, in the hormone regimens used, and in the populations studied.<ref name="Grodstein-2003">{{Cite journal |vauthors=Grodstein F, Clarkson TB, Manson JE |date=February 2003 |title=Understanding the divergent data on postmenopausal hormone therapy |journal=The New England Journal of Medicine |volume=348 |issue=7 |pages=645–650 |doi=10.1056/NEJMsb022365 |pmid=12584376}}</ref><ref name="Vandenbroucke-2009">{{Cite journal |vauthors=Vandenbroucke JP |date=April 2009 |title=The HRT controversy: observational studies and RCTs fall in line |journal=Lancet |volume=373 |issue=9671 |pages=1233–1235 |doi=10.1016/S0140-6736(09)60708-X |pmid=19362661 |s2cid=44991220}}</ref> The use of hormone replacement therapy decreased after publication of the RCTs.<ref name="Hsu-2009">{{Cite journal |vauthors=Hsu A, Card A, Lin SX, Mota S, Carrasquillo O, Moran A |date=December 2009 |title=Changes in postmenopausal hormone replacement therapy use among women with high cardiovascular risk |journal=American Journal of Public Health |volume=99 |issue=12 |pages=2184–2187 |doi=10.2105/AJPH.2009.159889 |pmc=2775780 |pmid=19833984}}</ref>