Editing Randomized controlled trial (section)

== Disadvantages ==
Many papers discuss the disadvantages of RCTs.<ref name="Black-1996">{{Cite journal |vauthors=Black N |date=May 1996 |title=Why we need observational studies to evaluate the effectiveness of health care |journal=BMJ |volume=312 |issue=7040 |pages=1215–1218 |doi=10.1136/bmj.312.7040.1215 |pmc=2350940 |pmid=8634569}}</ref><ref name="Bell & Peck-2012">{{Cite journal |vauthors=Bell SH, Peck LR |year=2012 |title=Obstacles to and limitations of social experiments: 15 false alarms |url=http://abtassociates.com/white-papers/2012/obstacles-to-and-limitations-of-social-experiments.aspx |journal=Abt Thought Leadership Paper Series}}</ref><ref name="Sanson-Fisher-2007">{{Cite journal |vauthors=Sanson-Fisher RW, Bonevski B, Green LW, D'Este C |date=August 2007 |title=Limitations of the randomized controlled trial in evaluating population-based health interventions |journal=American Journal of Preventive Medicine |volume=33 |issue=2 |pages=155–161 |doi=10.1016/j.amepre.2007.04.007 |pmid=17673104}}</ref>   Among the most frequently cited drawbacks are:

=== Time and costs ===
RCTs can be expensive;<ref name="Sanson-Fisher-2007" /> one study found 28 [[Phase III clinical trials|Phase III]] RCTs funded by the [[National Institute of Neurological Disorders and Stroke]] prior to 2000 with a total cost of US$335 million,<ref name="Johnston-2006">{{Cite journal |vauthors=Johnston SC, Rootenberg JD, Katrak S, Smith WS, Elkins JS |date=April 2006 |title=Effect of a US National Institutes of Health programme of clinical trials on public health and costs |journal=Lancet |volume=367 |issue=9519 |pages=1319–1327 |doi=10.1016/S0140-6736(06)68578-4 |pmid=16631910 |s2cid=41035177}}</ref> for a [[mean]] cost of US$12 million per RCT.  Nevertheless, the [[return on investment]] of RCTs may be high, in that the same study projected that the 28 RCTs produced a "net benefit to society at 10-years" of 46 times the cost of the trials program, based on evaluating a [[quality-adjusted life year]] as equal to the prevailing mean [[per capita]] [[gross domestic product]].<ref name="Johnston-2006" />

The conduct of an RCT takes several years until being published; thus, data is restricted from the medical community for long years and may be of less relevance at time of publication.<ref name="CaseReport">{{Cite journal |vauthors=Yitschaky O, Yitschaky M, Zadik Y |date=May 2011 |title=Case report on trial: Do you, Doctor, swear to tell the truth, the whole truth and nothing but the truth? |journal=Journal of Medical Case Reports |volume=5 |issue=1 |page=179 |doi=10.1186/1752-1947-5-179 |pmc=3113995 |pmid=21569508 |doi-access=free}}</ref>

It is costly to maintain RCTs for the years or decades that would be ideal for evaluating some interventions.<ref name="Black-1996" /><ref name="Sanson-Fisher-2007" />

Interventions to prevent events that occur only infrequently (e.g., [[sudden infant death syndrome]]) and uncommon adverse outcomes (e.g., a rare side effect of a drug) would require RCTs with extremely large sample sizes and may, therefore, best be assessed by observational studies.<ref name="Black-1996" />

Due to the costs of running RCTs, these usually only inspect one variable or very few variables, rarely reflecting the full picture of a complicated medical situation; whereas the [[case report]], for example, can detail many aspects of the patient's [[medicine|medical]] situation (e.g. [[patient history]], [[physical examination]], [[diagnosis]], [[psychosocial]] aspects, follow up).<ref name="CaseReport" />

=== Conflict of interest dangers ===

A 2011 study done to disclose possible [[conflicts of interest]]s in underlying research studies used for medical meta-analyses reviewed 29 meta-analyses and found that conflicts of interests in the studies underlying the meta-analyses were rarely disclosed.  The 29 meta-analyses included 11 from general medicine journals; 15 from specialty medicine journals, and 3 from the [[Cochrane Collaboration|Cochrane]] Database of Systematic Reviews. The 29 meta-analyses reviewed an aggregate of 509 randomized controlled trials (RCTs). Of these, 318 RCTs reported funding sources with 219 (69%) industry funded. 132 of the 509 RCTs reported author conflict of interest disclosures, with 91 studies (69%) disclosing industry financial ties with one or more authors. The information was, however, seldom reflected in the meta-analyses. Only two (7%) reported RCT funding sources and none reported RCT author-industry ties. The authors concluded "without acknowledgment of COI due to industry funding or author industry financial ties from RCTs included in meta-analyses, readers' understanding and appraisal of the evidence from the meta-analysis may be compromised."<ref>{{Cite web |title=How Well Do Meta-Analyses Disclose Conflicts of Interests in Underlying Research Studies &#124; The Cochrane Collaboration |url=http://www.cochrane.org/news/blog/how-well-do-meta-analyses-disclose-conflicts-interests-underlying-research-studies |archive-url=https://web.archive.org/web/20141216145035/http://www.cochrane.org/news/blog/how-well-do-meta-analyses-disclose-conflicts-interests-underlying-research-studies |archive-date=2014-12-16 |access-date=2011-08-19 |publisher=Cochrane.org}}</ref>

Some RCTs are fully or partly funded by the health care industry (e.g., the [[pharmaceutical industry]]) as opposed to government, nonprofit, or other sources. A systematic review published in 2003 found four 1986–2002 articles comparing industry-sponsored and nonindustry-sponsored RCTs, and in all the articles there was a correlation of industry sponsorship and positive study outcome.<ref name="Bekelman-2003">{{Cite journal |vauthors=Bekelman JE, Li Y, Gross CP |year=2003 |title=Scope and impact of financial conflicts of interest in biomedical research: a systematic review |journal=JAMA |volume=289 |issue=4 |pages=454–465 |doi=10.1001/jama.289.4.454 |pmid=12533125}}</ref> A 2004 study of 1999–2001 RCTs published in leading medical and surgical journals determined that industry-funded RCTs "are more likely to be associated with statistically significant pro-industry findings."<ref name="Bhandari-2004">{{Cite journal |vauthors=Bhandari M, Busse JW, Jackowski D, Montori VM, Schünemann H, Sprague S, Mears D, Schemitsch EH, Heels-Ansdell D, Devereaux PJ |date=February 2004 |title=Association between industry funding and statistically significant pro-industry findings in medical and surgical randomized trials |url=http://ecmaj.com/cgi/content/full/170/4/477 |journal=CMAJ |volume=170 |issue=4 |pages=477–480 |pmc=332713 |pmid=14970094}}</ref> These results have been mirrored in trials in surgery, where although industry funding did not affect the rate of trial discontinuation it was however associated with a lower odds of publication for completed trials.<ref name="Chapman-2014">{{Cite journal |vauthors=Chapman SJ, Shelton B, Mahmood H, Fitzgerald JE, Harrison EM, Bhangu A |date=December 2014 |title=Discontinuation and non-publication of surgical randomised controlled trials: observational study |journal=BMJ |volume=349 |pages=g6870 |doi=10.1136/bmj.g6870 |pmc=4260649 |pmid=25491195}}</ref> One possible reason for the pro-industry results in industry-funded published RCTs is [[publication bias]].<ref name="Bhandari-2004" />  Other authors have cited the differing goals of academic and industry sponsored research as contributing to the difference. Commercial sponsors may be more focused on performing trials of drugs that have already shown promise in early stage trials, and on replicating previous positive results to fulfill regulatory requirements for drug approval.<ref>{{Cite journal |vauthors=Ridker PM, Torres J |date=May 2006 |title=Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-for-profit organizations: 2000-2005 |journal=JAMA |volume=295 |issue=19 |pages=2270–2274 |doi=10.1001/jama.295.19.2270 |pmid=16705108 |doi-access=free}}</ref>

=== Ethics ===
If a [[disruptive innovation]] in medical technology is developed, it may be difficult to test this ethically in an RCT if it becomes "obvious" that the control subjects have poorer outcomes—either due to other foregoing testing, or within the initial phase of the RCT itself.  Ethically it may be necessary to abort the RCT prematurely, and getting ethics approval (and patient agreement) to withhold the innovation from the control group in future RCTs may not be feasible.{{cn|date=November 2023}}

Historical control trials (HCT) exploit the data of previous RCTs to reduce the sample size; however, these approaches are controversial in the scientific community and must be handled with care.<ref>{{Cite journal |vauthors=Zhang S, Cao J, Ahn C |date=August 2010 |title=Calculating sample size in trials using historical controls |journal=Clinical Trials |volume=7 |issue=4 |pages=343–353 |doi=10.1177/1740774510373629 |pmc=3085081 |pmid=20573638}}</ref>