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第68行： − + − − 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. However, trial registration may still occur late or not at all. − − 2004年， http://www.ICMJE.org/医学杂志编辑国际委员会(ICMJE)宣布，所有在2005年7月1日之后开始注册的试验必须在考虑在委员会12个成员之一的杂志上发表之前注册。然而，试验登记可能仍然延迟或根本不会发生。 − − − − Medical journals have been slow in adapting policies requiring mandatory clinical trial registration as a prerequisite for publication. − − 医学期刊在适应将强制性临床试验登记作为发表的先决条件的政策方面进展缓慢。 第110行：
第100行： − An analysis of the 616 RCTs indexed in PubMed during December 2006 found that 78% were parallel-group trials, 16% were crossover, 2% were split-body, 2% were cluster, and 2% were factorial. Explanatory RCTs test efficacy in a research setting with highly selected participants and under highly controlled conditions. Most RCTs are superiority trials, in which one intervention is hypothesized to be superior to another in a statistically significant way. − − 对2006年12月在 PubMed 收录的616例随机对照试验的分析发现，78% 为平行组试验，16% 为交叉组试验，2% 为分体组试验，2% 为聚类组试验，2% 为因子组试验。解释性随机对照试验在高度选择参与者和高度控制条件下的研究环境中测试效力。大多数随机对照试验是优势试验，其中一种干预假设在统计学意义上优于另一种干预。 第119行：
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第128行： + + + + + + − An ideal randomization procedure would achieve the following goals: − 一个理想的随机化程序将实现以下目标:+ + + 第156行：
第152行： − However, no single randomization procedure meets those goals in every circumstance, so researchers must select a procedure for a given study based on its advantages and disadvantages.+ − − 然而，没有一个单一的随机化程序在每种情况下都能满足这些目标，因此研究人员必须根据其优点和缺点来选择一个给定的研究程序。 − + − {{cite book | last = Vonesh | first = Edward F. |author2=Chinchilli, Vernon G. | chapter=Crossover Experiments| pages=111–202|title = Linear and Nonlinear Models for the Analysis of Repeated Measurements | publisher = London: Chapman and Hall | year = 1997 }}</ref> − − This is a commonly used and intuitive procedure, similar to "repeated fair coin-tossing." − − 这是一个常用且直观的过程，类似于“反复公平地掷硬币” 第175行：
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第181行： − + − − “分配隐藏”(定义为“保护随机化过程的程序，以便在病人进入研究之前不知道要分配的治疗”)在随机对照试验中很重要。在实践中，临床研究人员在随机对照试验中常常发现难以保持公正性。关于调查人员将密封的信封举到灯光下或者搜查办公室来决定团队任务，以便指定下一个病人的任务的故事比比皆是。这种做法引入了选择偏差和混杂因素(这两者都应该通过随机化来减少) ，可能会扭曲研究结果。另一方面，2008年的一项对146项元分析的研究得出结论，分配隐瞒不充分或不明确的随机对照试验的结果往往只有在随机对照试验的结果是主观的而不是客观的情况下才会偏向于有益的结果。 − 第198行：
第188行： + − The number of treatment units (subjects or groups of subjects) assigned to control and treatment groups, affects an RCT's reliability. If the effect of the treatment is small, the number of treatment units in either group may be insufficient for rejecting the null hypothesis in the respective statistical test. The failure to reject the null hypothesis would imply that the treatment shows no statistically significant effect on the treated in a given test. But as the sample size increases, the same RCT may be able to demonstrate a significant effect of the treatment, even if this effect is small. − − 分配给控制组和治疗组的治疗单位(受试者或受试者组)的数量影响 RCT 的可靠性。如果治疗的效果很小，任何一组的治疗单位的数量都可能不足以在各自的统计检验中拒绝无效假设。拒绝零假设的失败将意味着治疗在给定的测试中对治疗没有统计学意义上的显著影响。但是随着样本量的增加，相同的随机对照试验也许能够证明治疗的显著效果，即使这种效果很小。 第225行：
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第337行： + − 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. 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." 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. One possible reason for the pro-industry results in industry-funded published RCTs is publication bias.+ − 有些 rct 完全或部分由医疗保健行业(如制药行业)资助，而不是政府、非营利组织或其他来源。2003年发表的一份系统综述研究报告发现，1986年至2002年间，有4篇文章比较了行业赞助和非行业赞助的 rct，在所有的文章中，行业赞助和正面研究结果之间存在相关性。2004年发表在主要医学和外科杂志上的一项关于1999-2001年的 rct 的研究表明，工业资助的 rct“更有可能与具有统计学意义的有利于工业的发现相关联。”这些结果已经反映在手术试验中，虽然行业资金并不影响试验中止率，但是与完成试验的发表机率较低相关。支持产业的结果在产业资助的已发表的研究报告中出现的一个可能的原因是出版偏见。 第366行：
第368行： − Due to the recent emergence of RCTs in social science, the use of RCTs in social sciences is a contested issue. Some writers from a medical or health background have argued that existing research in a range of social science disciplines lacks rigour, and should be improved by greater use of randomized control trials. − − 由于最近在社会科学中出现了 rct，rct 在社会科学中的应用是一个有争议的问题。一些有医学或健康背景的作家认为，一系列社会科学学科的现有研究缺乏严谨性，应该通过更多地使用随机对照试验来改进。 第378行：
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第452行： − Have a stable and predictable relationship to exogenous factors+ 第539行：
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第570行： − − === Conflict of interest dangers === 第562行：
第581行： − 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|url=http://www.cochrane.org/news/blog/how-well-do-meta-analyses-disclose-conflicts-interests-underlying-research-studies |title=How Well Do Meta-Analyses Disclose Conflicts of Interests in Underlying Research Studies | The Cochrane Collaboration |publisher=Cochrane.org |access-date=2011-08-19}}</ref> 第573行：
第591行： − − 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 | title = Scope and impact of financial conflicts of interest in biomedical research: a systematic review | journal = [[J Am Med Assoc]] | volume = 289 | issue = 4 | pages = 454–65 | year = 2003 | pmid = 12533125 | doi = 10.1001/jama.289.4.454 }}</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 | title = Association between industry funding and statistically significant pro-industry findings in medical and surgical randomized trials | journal = [[Can Med Assoc J]] | volume = 170 | issue = 4 | pages = 477–80 | year = 2004 | url = http://ecmaj.com/cgi/content/full/170/4/477 | pmid = 14970094 | pmc = 332713 }}</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 | title = Discontinuation and non-publication of surgical randomised controlled trials: observational study | journal = [[BMJ]] | volume = 349 | page = g6870| year = 2014 | pmid = 25491195 | pmc = 4260649 | doi=10.1136/bmj.g6870}}</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 |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=2270–4 |year=2006 |pmid=16705108 |doi=10.1001/jama.295.19.2270 |doi-access=free }}</ref> −
无编辑摘要
<blockquote>
<blockquote>
Ronald A. Fisher was "interested in application and in the popularization of statistical methods and his early book ''[[Statistical Methods for Research Workers]]'', published in 1925, went through many editions and motivated and influenced the practical use of statistics in many fields of study. His ''Design of Experiments'' (1935) <!-- was also crucially fundamental in the promotion of--> [promoted] statistical technique and application. In that book he emphasized examples and how to design experiments systematically from a statistical point of view. The mathematical justification of the methods described was not stressed and, indeed, proofs were often barely sketched
Ronald A. Fisher was "interested in application and in the popularization of statistical methods and his early book ''[[Statistical Methods for Research Workers]]'', published in 1925, went through many editions and motivated and influenced the practical use of statistics in many fields of study. His ''Design of Experiments'' (1935) <!-- was also crucially fundamental in the promotion of--> [promoted] statistical technique and application. In that book he emphasized examples and how to design experiments systematically from a statistical point of view. The mathematical justification of the methods described was not stressed and, indeed, proofs were often barely sketched or omitted altogether ..., a fact which led [[Henry Mann|H. B. Mann]] to fill the gaps with a rigorous mathematical treatment in his well known treatise, {{harvtxt|Mann|1949}}."
or omitted altogether ..., a fact which led [[Henry Mann|H. B. Mann]] to fill the gaps with a rigorous mathematical treatment in his well known treatise, {{harvtxt|Mann|1949}}."
</blockquote>
</blockquote>
== Ethics ==
== Ethics ==
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 | title = The therapeutic misconception: informed consent in psychiatric research | journal = [[Int J Law Psychiatry]] | volume = 5 | issue = 3–4 | pages = 319–29 | year = 1982 | 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 | title = Clinical trials and medical care: defining the therapeutic misconception | journal = [[PLoS Med]] | volume = 4 | issue = 11 | pages = e324 | year = 2007 | doi = 10.1371/journal.pmed.0040324 | pmid = 18044980 | pmc = 2082641 }}</ref> Further research is necessary to determine the prevalence of and ways to address this "[[therapeutic misconception]]".<ref name="Henderson-2007"/>
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 | title = The therapeutic misconception: informed consent in psychiatric research | journal = [[Int J Law Psychiatry]] | volume = 5 | issue = 3–4 | pages = 319–29 | year = 1982 | 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 | title = Clinical trials and medical care: defining the therapeutic misconception | journal = [[PLoS Med]] | volume = 4 | issue = 11 | pages = e324 | year = 2007 | doi = 10.1371/journal.pmed.0040324 | pmid = 18044980 | pmc = 2082641 }}</ref> Further research is necessary to determine the prevalence of and ways to address this "[[therapeutic misconception]]".<ref name="Henderson-2007"/>
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. Further research is necessary to determine the prevalence of and ways to address this "therapeutic misconception". For example, patients with terminal illness may join trials in the hope of being cured, even when treatments are unlikely to be successful.
尽管受试者几乎总是在知情的情况下同意参加随机对照试验，但自1982年以来的研究记录表明，随机对照试验的受试者可能认为他们肯定会接受对他们个人最好的治疗; 也就是说，他们不理解研究和治疗之间的区别。需要进一步研究，以确定这种”治疗性误解”的流行程度和解决方法。例如，患有晚期疾病的病人可能会加入临床试验，希望治愈，即使治疗不太可能成功。
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, etal |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=1250–1 |date=September 2004 |pmid=15356289 |doi=10.1056/NEJMe048225 }}</ref> However, trial registration may still occur late or not at all.<ref name="pmid22147862">{{cite journal|vauthors=Law MR, Kawasumi Y, Morgan SG | title=Despite law, fewer than one in eight completed studies of drugs and biologics are reported on time on ClinicalTrials.gov. | journal=Health Aff (Millwood) | year= 2011 | volume= 30 | issue= 12 | pages= 2338–45 | 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 | title=Comparison of registered and published primary outcomes in randomized controlled trials. | journal=JAMA | year= 2009 | volume= 302 | issue= 9 | pages= 977–84 | doi=10.1001/jama.2009.1242 | pmid=19724045 | doi-access=free }}</ref>
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, etal |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=1250–1 |date=September 2004 |pmid=15356289 |doi=10.1056/NEJMe048225 }}</ref> However, trial registration may still occur late or not at all.<ref name="pmid22147862">{{cite journal|vauthors=Law MR, Kawasumi Y, Morgan SG | title=Despite law, fewer than one in eight completed studies of drugs and biologics are reported on time on ClinicalTrials.gov. | journal=Health Aff (Millwood) | year= 2011 | volume= 30 | issue= 12 | pages= 2338–45 | 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 | title=Comparison of registered and published primary outcomes in randomized controlled trials. | journal=JAMA | year= 2009 | volume= 302 | issue= 9 | pages= 977–84 | doi=10.1001/jama.2009.1242 | pmid=19724045 | doi-access=free }}</ref>
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. However, trial registration may still occur late or not at all.
2004年， http://www.ICMJE.org/医学杂志编辑国际委员会(ICMJE)宣布，所有在2005年7月1日之后开始注册的试验必须在考虑在委员会12个成员之一的杂志上发表之前注册。然而，试验登记可能仍然延迟或根本不会发生。
Medical journals have been slow in adapting policies requiring mandatory clinical trial registration as a prerequisite for publication.<ref>{{cite journal|last1=Bhaumik|first1=S|title=Editorial policies of MEDLINE indexed Indian journals on clinical trial registration.|journal=Indian Pediatr.|date=Mar 2013|volume=50|issue=3|pages=339–40|pmid=23680610|doi=10.1007/s13312-013-0092-2|s2cid=40317464}}</ref>
Medical journals have been slow in adapting policies requiring mandatory clinical trial registration as a prerequisite for publication.<ref>{{cite journal|last1=Bhaumik|first1=S|title=Editorial policies of MEDLINE indexed Indian journals on clinical trial registration.|journal=Indian Pediatr.|date=Mar 2013|volume=50|issue=3|pages=339–40|pmid=23680610|doi=10.1007/s13312-013-0092-2|s2cid=40317464}}</ref>
Medical journals have been slow in adapting policies requiring mandatory clinical trial registration as a prerequisite for publication.
医学期刊在适应将强制性临床试验登记作为发表的先决条件的政策方面进展缓慢。
One way to classify RCTs is by [[study design]]. From most to least common in the healthcare literature, the major categories of RCT study designs are:<ref name="Hopewell-2010">{{Cite journal |vauthors=Hopewell S, Dutton S, Yu LM, Chan AW, Altman DG | title = The quality of reports of randomised trials in 2000 and 2006: comparative study of articles indexed in PubMed | journal = BMJ | volume = 340 | pages = c723 | year = 2010 | doi = 10.1136/bmj.c723 | pmid = 20332510 | pmc = 2844941 }}</ref>
One way to classify RCTs is by [[study design]]. From most to least common in the healthcare literature, the major categories of RCT study designs are:<ref name="Hopewell-2010">{{Cite journal |vauthors=Hopewell S, Dutton S, Yu LM, Chan AW, Altman DG | title = The quality of reports of randomised trials in 2000 and 2006: comparative study of articles indexed in PubMed | journal = BMJ | volume = 340 | pages = c723 | year = 2010 | doi = 10.1136/bmj.c723 | pmid = 20332510 | pmc = 2844941 }}</ref>
对 RCT 进行分类的一种方法是通过研究设计。从医疗保健文献中最常见到最不常见，RCT 研究设计的主要类别是
* [[Parallel study|Parallel-group]] – each participant is randomly assigned to a group, and all the participants in the group receive (or do not receive) an intervention.<ref>{{cite journal |last1=Kaiser |first1=Joerg |last2=Niesen |first2=Willem |last3=Probst |first3=Pascal |last4=Bruckner |first4=Thomas |last5=Doerr-Harim |first5=Colette |last6=Strobel |first6=Oliver |last7=Knebel |first7=Phillip |last8=Diener |first8=Markus K. |last9=Mihaljevic |first9=André L. |last10=Büchler |first10=Markus W. |last11=Hackert |first11=Thilo |title=Abdominal drainage versus no drainage after distal pancreatectomy: study protocol for a randomized controlled trial |journal=Trials |date=7 June 2019 |volume=20 |issue=1 |page=332 |doi=10.1186/s13063-019-3442-0|pmid=31174583 |pmc=6555976 |doi-access=free }}</ref><ref>{{cite journal |last1=Farag |first1=Sara M. |last2=Mohammed |first2=Manal O. |last3=EL-Sobky |first3=Tamer A. |last4=ElKadery |first4=Nadia A. |last5=ElZohiery |first5=Abeer K. |title=Botulinum Toxin A Injection in Treatment of Upper Limb Spasticity in Children with Cerebral Palsy: A Systematic Review of Randomized Controlled Trials |journal=JBJS Reviews |date=March 2020 |volume=8 |issue=3 |pages=e0119 |doi=10.2106/JBJS.RVW.19.00119 |pmid=32224633|pmc=7161716 |doi-access=free }}</ref>
* [[Parallel study|Parallel-group]] – each participant is randomly assigned to a group, and all the participants in the group receive (or do not receive) an intervention.<ref>{{cite journal |last1=Kaiser |first1=Joerg |last2=Niesen |first2=Willem |last3=Probst |first3=Pascal |last4=Bruckner |first4=Thomas |last5=Doerr-Harim |first5=Colette |last6=Strobel |first6=Oliver |last7=Knebel |first7=Phillip |last8=Diener |first8=Markus K. |last9=Mihaljevic |first9=André L. |last10=Büchler |first10=Markus W. |last11=Hackert |first11=Thilo |title=Abdominal drainage versus no drainage after distal pancreatectomy: study protocol for a randomized controlled trial |journal=Trials |date=7 June 2019 |volume=20 |issue=1 |page=332 |doi=10.1186/s13063-019-3442-0|pmid=31174583 |pmc=6555976 |doi-access=free }}</ref><ref>{{cite journal |last1=Farag |first1=Sara M. |last2=Mohammed |first2=Manal O. |last3=EL-Sobky |first3=Tamer A. |last4=ElKadery |first4=Nadia A. |last5=ElZohiery |first5=Abeer K. |title=Botulinum Toxin A Injection in Treatment of Upper Limb Spasticity in Children with Cerebral Palsy: A Systematic Review of Randomized Controlled Trials |journal=JBJS Reviews |date=March 2020 |volume=8 |issue=3 |pages=e0119 |doi=10.2106/JBJS.RVW.19.00119 |pmid=32224633|pmc=7161716 |doi-access=free }}</ref>
* [[Crossover study|Crossover]] – over time, each participant receives (or does not receive) an intervention in a random sequence.<ref>{{cite book | last = Jones | first = Byron |author2=Kenward, Michael G. | title = Design and Analysis of Cross-Over Trials | edition=Second| publisher = London: Chapman and Hall | year = 2003 }}</ref><ref>
* [[Crossover study|Crossover]] – over time, each participant receives (or does not receive) an intervention in a random sequence.<ref>{{cite book | last = Jones | first = Byron |author2=Kenward, Michael G. | title = Design and Analysis of Cross-Over Trials | edition=Second| publisher = London: Chapman and Hall | year = 2003 }}</ref><ref>{{cite book | last = Vonesh | first = Edward F. |author2=Chinchilli, Vernon G. | chapter=Crossover Experiments| pages=111–202|title = Linear and Nonlinear Models for the Analysis of Repeated Measurements | publisher = London: Chapman and Hall | year = 1997 }}</ref>
* [[Cluster randomised controlled trial|Cluster]] – pre-existing groups of participants (e.g., villages, schools) are randomly selected to receive (or not receive) an intervention.<ref>{{cite journal |last1=Gall |first1=Stefanie |last2=Adams |first2=Larissa |last3=Joubert |first3=Nandi |last4=Ludyga |first4=Sebastian |last5=Müller |first5=Ivan |last6=Nqweniso |first6=Siphesihle |last7=Pühse |first7=Uwe |last8=du Randt |first8=Rosa |last9=Seelig |first9=Harald |last10=Smith |first10=Danielle |last11=Steinmann |first11=Peter |last12=Utzinger |first12=Jürg |last13=Walter |first13=Cheryl |last14=Gerber |first14=Markus |last15=van Wouwe |first15=Jacobus P. |title=Effect of a 20-week physical activity intervention on selective attention and academic performance in children living in disadvantaged neighborhoods: A cluster randomized control trial |journal=PLOS ONE |date=8 November 2018 |volume=13 |issue=11 |pages=e0206908 |doi=10.1371/journal.pone.0206908 |pmid=30408073|pmc=6224098 |bibcode=2018PLoSO..1306908G |doi-access=free }}</ref><ref>{{cite journal |last1=Gladstone |first1=Melissa J. |last2=Chandna |first2=Jaya |last3=Kandawasvika |first3=Gwendoline |last4=Ntozini |first4=Robert |last5=Majo |first5=Florence D. |last6=Tavengwa |first6=Naume V. |last7=Mbuya |first7=Mduduzi N. N. |last8=Mangwadu |first8=Goldberg T. |last9=Chigumira |first9=Ancikaria |last10=Chasokela |first10=Cynthia M. |last11=Moulton |first11=Lawrence H. |last12=Stoltzfus |first12=Rebecca J. |last13=Humphrey |first13=Jean H. |last14=Prendergast |first14=Andrew J. |last15=Tumwine |first15=James K. |title=Independent and combined effects of improved water, sanitation, and hygiene (WASH) and improved complementary feeding on early neurodevelopment among children born to HIV-negative mothers in rural Zimbabwe: Substudy of a cluster-randomized trial |journal=PLOS Medicine |date=21 March 2019 |volume=16 |issue=3 |pages=e1002766 |doi=10.1371/journal.pmed.1002766|pmid=30897095 |pmc=6428259 |doi-access=free }}</ref>
* [[Cluster randomised controlled trial|Cluster]] – pre-existing groups of participants (e.g., villages, schools) are randomly selected to receive (or not receive) an intervention.<ref>{{cite journal |last1=Gall |first1=Stefanie |last2=Adams |first2=Larissa |last3=Joubert |first3=Nandi |last4=Ludyga |first4=Sebastian |last5=Müller |first5=Ivan |last6=Nqweniso |first6=Siphesihle |last7=Pühse |first7=Uwe |last8=du Randt |first8=Rosa |last9=Seelig |first9=Harald |last10=Smith |first10=Danielle |last11=Steinmann |first11=Peter |last12=Utzinger |first12=Jürg |last13=Walter |first13=Cheryl |last14=Gerber |first14=Markus |last15=van Wouwe |first15=Jacobus P. |title=Effect of a 20-week physical activity intervention on selective attention and academic performance in children living in disadvantaged neighborhoods: A cluster randomized control trial |journal=PLOS ONE |date=8 November 2018 |volume=13 |issue=11 |pages=e0206908 |doi=10.1371/journal.pone.0206908 |pmid=30408073|pmc=6224098 |bibcode=2018PLoSO..1306908G |doi-access=free }}</ref><ref>{{cite journal |last1=Gladstone |first1=Melissa J. |last2=Chandna |first2=Jaya |last3=Kandawasvika |first3=Gwendoline |last4=Ntozini |first4=Robert |last5=Majo |first5=Florence D. |last6=Tavengwa |first6=Naume V. |last7=Mbuya |first7=Mduduzi N. N. |last8=Mangwadu |first8=Goldberg T. |last9=Chigumira |first9=Ancikaria |last10=Chasokela |first10=Cynthia M. |last11=Moulton |first11=Lawrence H. |last12=Stoltzfus |first12=Rebecca J. |last13=Humphrey |first13=Jean H. |last14=Prendergast |first14=Andrew J. |last15=Tumwine |first15=James K. |title=Independent and combined effects of improved water, sanitation, and hygiene (WASH) and improved complementary feeding on early neurodevelopment among children born to HIV-negative mothers in rural Zimbabwe: Substudy of a cluster-randomized trial |journal=PLOS Medicine |date=21 March 2019 |volume=16 |issue=3 |pages=e1002766 |doi=10.1371/journal.pmed.1002766|pmid=30897095 |pmc=6428259 |doi-access=free }}</ref>
An analysis of the 616 RCTs indexed in [[PubMed]] during December 2006 found that 78% were parallel-group trials, 16% were crossover, 2% were split-body, 2% were cluster, and 2% were factorial.<ref name="Hopewell-2010"/>
An analysis of the 616 RCTs indexed in [[PubMed]] during December 2006 found that 78% were parallel-group trials, 16% were crossover, 2% were split-body, 2% were cluster, and 2% were factorial.<ref name="Hopewell-2010"/>
An analysis of the 616 RCTs indexed in PubMed during December 2006 found that 78% were parallel-group trials, 16% were crossover, 2% were split-body, 2% were cluster, and 2% were factorial.
对2006年12月在 PubMed 收录的616例随机对照试验的分析发现，78% 为平行组试验，16% 为交叉组试验，2% 为分体组试验，2% 为聚类组试验，2% 为因子组试验。解释性随机对照试验在高度选择参与者和高度控制条件下的研究环境中测试效力。大多数随机对照试验是优势试验，其中一种干预假设在统计学意义上优于另一种干预。
To balance group sizes in smaller RCTs, some form of "restricted" randomization is recommended.
To balance group sizes in smaller RCTs, some form of "restricted" randomization is recommended.
RCTs can be classified as "explanatory" or "pragmatic."<ref name="Zwarenstein-2008">{{Cite journal | author = Zwarenstein M, Treweek S, Gagnier JJ, Altman DG, Tunis S, Haynes B, Oxman AD, Moher D; CONSORT group; Pragmatic Trials in Healthcare (Practihc) group | title = Improving the reporting of pragmatic trials: an extension of the CONSORT statement | journal = BMJ | volume = 337 | pages = a2390 | year = 2008 | doi = 10.1136/bmj.a2390 | pmid = 19001484 | pmc=3266844}}</ref> Explanatory RCTs test [[Efficacy#Medicine|efficacy]] in a research setting with highly selected participants and under highly controlled conditions.<ref name="Zwarenstein-2008"/> In contrast, pragmatic RCTs (pRCTs) test [[Effectiveness#Usage|effectiveness]] in everyday practice with relatively unselected participants and under flexible conditions; in this way, pragmatic RCTs can "inform decisions about practice."<ref name="Zwarenstein-2008"/>
RCTs can be classified as "explanatory" or "pragmatic."<ref name="Zwarenstein-2008">{{Cite journal | author = Zwarenstein M, Treweek S, Gagnier JJ, Altman DG, Tunis S, Haynes B, Oxman AD, Moher D; CONSORT group; Pragmatic Trials in Healthcare (Practihc) group | title = Improving the reporting of pragmatic trials: an extension of the CONSORT statement | journal = BMJ | volume = 337 | pages = a2390 | year = 2008 | doi = 10.1136/bmj.a2390 | pmid = 19001484 | pmc=3266844}}</ref> Explanatory RCTs test [[Efficacy#Medicine|efficacy]] in a research setting with highly selected participants and under highly controlled conditions.<ref name="Zwarenstein-2008"/> In contrast, pragmatic RCTs (pRCTs) test [[Effectiveness#Usage|effectiveness]] in everyday practice with relatively unselected participants and under flexible conditions; in this way, pragmatic RCTs can "inform decisions about practice."<ref name="Zwarenstein-2008"/>
"Allocation concealment" (defined as "the procedure for protecting the randomization process so that the treatment to be allocated is not known before the patient is entered into the study") is important in RCTs. In practice, clinical investigators in RCTs often find it difficult to maintain impartiality. Stories abound of investigators holding up sealed envelopes to lights or ransacking offices to determine group assignments in order to dictate the assignment of their next patient. Such practices introduce selection bias and confounders (both of which should be minimized by randomization), possibly distorting the results of the study. On the other hand, a 2008 study of 146 meta-analyses concluded that the results of RCTs with inadequate or unclear allocation concealment tended to be biased toward beneficial effects only if the RCTs' outcomes were subjective as opposed to objective.
RCTs can be classified as "explanatory" or "pragmatic."[42] Explanatory RCTs test efficacy in a research setting with highly selected participants and under highly controlled conditions.[42] In contrast, pragmatic RCTs (pRCTs) test effectiveness in everyday practice with relatively unselected participants and under flexible conditions; in this way, pragmatic RCTs can "inform decisions about practice."
Another classification of RCTs categorizes them as "superiority trials", "noninferiority trials", and "equivalence trials", which differ in methodology and reporting.<ref name="Piaggio-2006">{{Cite journal | author = Piaggio G, Elbourne DR, [[Doug Altman|Altman DG]], [[Stuart Pocock|Pocock SJ]], Evans SJ; CONSORT Group | title = Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement | journal = JAMA | volume = 295 | issue = 10 | pages = 1152–60 | year = 2006 | doi = 10.1001/jama.295.10.1152 | pmid = 16522836 | url = http://researchonline.lshtm.ac.uk/12069/1/Reporting%20of%20Noninferiority%20and%20Equivalence%20Randomized%20Trials.pdf }}</ref> Most RCTs are superiority trials, in which one intervention is hypothesized to be superior to another in a [[Statistical significance|statistically significant]] way.<ref name="Piaggio-2006"/> Some RCTs are noninferiority trials "to determine whether a new treatment is no worse than a reference treatment."<ref name="Piaggio-2006"/> Other RCTs are equivalence trials in which the hypothesis is that two interventions are indistinguishable from each other.<ref name="Piaggio-2006"/>
Another classification of RCTs categorizes them as "superiority trials", "noninferiority trials", and "equivalence trials", which differ in methodology and reporting.<ref name="Piaggio-2006">{{Cite journal | author = Piaggio G, Elbourne DR, [[Doug Altman|Altman DG]], [[Stuart Pocock|Pocock SJ]], Evans SJ; CONSORT Group | title = Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement | journal = JAMA | volume = 295 | issue = 10 | pages = 1152–60 | year = 2006 | doi = 10.1001/jama.295.10.1152 | pmid = 16522836 | url = http://researchonline.lshtm.ac.uk/12069/1/Reporting%20of%20Noninferiority%20and%20Equivalence%20Randomized%20Trials.pdf }}</ref> Most RCTs are superiority trials, in which one intervention is hypothesized to be superior to another in a [[Statistical significance|statistically significant]] way.<ref name="Piaggio-2006"/> Some RCTs are noninferiority trials "to determine whether a new treatment is no worse than a reference treatment."<ref name="Piaggio-2006"/> Other RCTs are equivalence trials in which the hypothesis is that two interventions are indistinguishable from each other.<ref name="Piaggio-2006"/>
Most RCTs are superiority trials, in which one intervention is hypothesized to be superior to another in a statistically significant way.
== Randomization ==
== Randomization ==
The advantages of proper [[randomized experiment|randomization]] in RCTs include:<ref name="SchulzGrimes2002">{{Cite journal |vauthors=Schulz KF, Grimes DA | title = Generation of allocation sequences in randomised trials: chance, not choice | journal = Lancet | volume = 359 | issue = 9305 | pages = 515–9 | year = 2002 | doi = 10.1016/S0140-6736(02)07683-3 | url =https://www.who.int/entity/rhl/LANCET_515-519.pdf | pmid = 11853818 | s2cid = 291300 }}</ref>
The advantages of proper [[randomized experiment|randomization]] in RCTs include:<ref name="SchulzGrimes2002">{{Cite journal |vauthors=Schulz KF, Grimes DA | title = Generation of allocation sequences in randomised trials: chance, not choice | journal = Lancet | volume = 359 | issue = 9305 | pages = 515–9 | year = 2002 | doi = 10.1016/S0140-6736(02)07683-3 | url =https://www.who.int/entity/rhl/LANCET_515-519.pdf | pmid = 11853818 | s2cid = 291300 }}</ref>
However empirical evidence that adequate randomization changes outcomes relative to inadequate randomization has been difficult to detect.<ref name="Howick-2014">{{Cite journal |vauthors=Howick J, Mebius A | title = In search of justification for the unpredictability paradox | journal = Trials | volume = 15 | pages = 480 | year = 2014 | doi = 10.1186/1745-6215-15-480 | pmid = 25490908 | pmc=4295227}}</ref>
However empirical evidence that adequate randomization changes outcomes relative to inadequate randomization has been difficult to detect.<ref name="Howick-2014">{{Cite journal |vauthors=Howick J, Mebius A | title = In search of justification for the unpredictability paradox | journal = Trials | volume = 15 | pages = 480 | year = 2014 | doi = 10.1186/1745-6215-15-480 | pmid = 25490908 | pmc=4295227}}</ref>
Regardless of the statistical methods used, important considerations in the analysis of RCT data include:
Regardless of the statistical methods used, important considerations in the analysis of RCT data include:
An ideal randomization procedure would achieve the following goals:<ref name="Lachin-1988a">{{Cite journal | author = Lachin JM | title = Statistical properties of randomization in clinical trials | journal = [[Controlled Clinical Trials]] | volume = 9 | issue = 4 | pages = 289–311 | year = 1988 | pmid = 3060315 | doi = 10.1016/0197-2456(88)90045-1 }}</ref>
An ideal randomization procedure would achieve the following goals:<ref name="Lachin-1988a">{{Cite journal | author = Lachin JM | title = Statistical properties of randomization in clinical trials | journal = [[Controlled Clinical Trials]] | volume = 9 | issue = 4 | pages = 289–311 | year = 1988 | pmid = 3060315 | doi = 10.1016/0197-2456(88)90045-1 }}</ref>
An ideal randomization procedure would achieve the following goals:
一个理想的随机化程序将实现以下目标:
Two studies published in The New England Journal of Medicine in 2000 found that observational studies and RCTs overall produced similar results. The authors of the 2000 findings questioned the belief that "observational studies should not be used for defining evidence-based medical care" and that RCTs' results are "evidence of the highest grade."
Two studies published in The New England Journal of Medicine in 2000 found that observational studies and RCTs overall produced similar results. The authors of the 2000 findings questioned the belief that "observational studies should not be used for defining evidence-based medical care" and that RCTs' results are "evidence of the highest grade."
However, no single randomization procedure meets those goals in every circumstance, so researchers must select a procedure for a given study based on its advantages and disadvantages.
However, no single randomization procedure meets those goals in every circumstance, so researchers must select a procedure for a given study based on its advantages and disadvantages.
However, no single randomization procedure meets those goals in every circumstance, so researchers must select a procedure for a given study based on its advantages and disadvantages.
然而，没有一个单一的随机化程序在每种情况下都能满足这些目标，因此研究人员必须根据其优点和缺点来选择一个给定的研究程序。
==== Simple ====
==== Simple ====
This is a commonly used and intuitive procedure, similar to "repeated fair coin-tossing."
这是一个常用且直观的过程，类似于“反复公平地掷硬币”
==== Restricted ====
==== Restricted ====
"Allocation concealment" (defined as "the procedure for protecting the randomization process so that the treatment to be allocated is not known before the patient is entered into the study") is important in RCTs.<ref name="Forder-2005">{{Cite journal |vauthors=Forder PM, Gebski VJ, Keech AC | title = Allocation concealment and blinding: when ignorance is bliss | journal = Med J Aust | volume = 182 | issue = 2 | pages = 87–9 | year = 2005 | url = http://www.mja.com.au/public/issues/182_02_170105/for10877_fm.html | pmid = 15651970 | doi = 10.5694/j.1326-5377.2005.tb06584.x | s2cid = 202149 }}</ref> In practice, clinical investigators in RCTs often find it difficult to maintain impartiality. Stories abound of investigators holding up sealed envelopes to lights or ransacking offices to determine group assignments in order to dictate the assignment of their next patient.<ref name="Schulz-2002">{{Cite journal | title = Allocation concealment in randomised trials: defending against deciphering | journal = Lancet | volume = 359 | issue = 9306 | pages = 614–8 | year = 2002 | doi = 10.1016/S0140-6736(02)07750-4 | url =https://www.who.int/entity/rhl/LANCET_614-618.pdf | pmid = 11867132 |vauthors=Schulz KF, Grimes DA | s2cid = 12902486 }}</ref> Such practices introduce selection bias and [[Lurking variable|confounders]] (both of which should be minimized by randomization), possibly distorting the results of the study.<ref name="Schulz-2002"/> Adequate allocation concealment should defeat patients and investigators from discovering treatment allocation once a study is underway and after the study has concluded. Treatment related side-effects or adverse events may be specific enough to reveal allocation to investigators or patients thereby introducing bias or influencing any subjective parameters collected by investigators or requested from subjects.
"Allocation concealment" (defined as "the procedure for protecting the randomization process so that the treatment to be allocated is not known before the patient is entered into the study") is important in RCTs.<ref name="Forder-2005">{{Cite journal |vauthors=Forder PM, Gebski VJ, Keech AC | title = Allocation concealment and blinding: when ignorance is bliss | journal = Med J Aust | volume = 182 | issue = 2 | pages = 87–9 | year = 2005 | url = http://www.mja.com.au/public/issues/182_02_170105/for10877_fm.html | pmid = 15651970 | doi = 10.5694/j.1326-5377.2005.tb06584.x | s2cid = 202149 }}</ref> In practice, clinical investigators in RCTs often find it difficult to maintain impartiality. Stories abound of investigators holding up sealed envelopes to lights or ransacking offices to determine group assignments in order to dictate the assignment of their next patient.<ref name="Schulz-2002">{{Cite journal | title = Allocation concealment in randomised trials: defending against deciphering | journal = Lancet | volume = 359 | issue = 9306 | pages = 614–8 | year = 2002 | doi = 10.1016/S0140-6736(02)07750-4 | url =https://www.who.int/entity/rhl/LANCET_614-618.pdf | pmid = 11867132 |vauthors=Schulz KF, Grimes DA | s2cid = 12902486 }}</ref> Such practices introduce selection bias and [[Lurking variable|confounders]] (both of which should be minimized by randomization), possibly distorting the results of the study.<ref name="Schulz-2002"/> Adequate allocation concealment should defeat patients and investigators from discovering treatment allocation once a study is underway and after the study has concluded. Treatment related side-effects or adverse events may be specific enough to reveal allocation to investigators or patients thereby introducing bias or influencing any subjective parameters collected by investigators or requested from subjects.
"Allocation concealment" (defined as "the procedure for protecting the randomization process so that the treatment to be allocated is not known before the patient is entered into the study") is important in RCTs. In practice, clinical investigators in RCTs often find it difficult to maintain impartiality. Stories abound of investigators holding up sealed envelopes to lights or ransacking offices to determine group assignments in order to dictate the assignment of their next patient. Such practices introduce selection bias and confounders (both of which should be minimized by randomization), possibly distorting the results of the study. On the other hand, a 2008 study of 146 meta-analyses concluded that the results of RCTs with inadequate or unclear allocation concealment tended to be biased toward beneficial effects only if the RCTs' outcomes were subjective as opposed to objective.
“分配隐藏”(定义为“保护随机化过程的程序，以便在病人进入研究之前不知道要分配的治疗”)在随机对照试验中很重要。在实践中，临床研究人员在随机对照试验中常常发现难以保持公正性。关于调查人员将密封的信封举到灯光下或者搜查办公室来决定团队任务，以便指定下一个病人的任务的故事比比皆是。这种做法引入了选择偏差和混杂因素(这两者都应该通过随机化来减少) ，可能会扭曲研究结果。另一方面，2008年的一项对146项元分析的研究得出结论，分配隐瞒不充分或不明确的随机对照试验的结果往往只有在随机对照试验的结果是主观的而不是客观的情况下才会偏向于有益的结果。
Many papers discuss the disadvantages of RCTs. Among the most frequently cited drawbacks are:
Many papers discuss the disadvantages of RCTs. Among the most frequently cited drawbacks are:
Some standard methods of ensuring allocation concealment include sequentially numbered, opaque, sealed envelopes (SNOSE); sequentially numbered containers; pharmacy controlled randomization; and central randomization.<ref name="Schulz-2002"/> It is recommended that allocation concealment methods be included in an RCT's [[Clinical trial protocol|protocol]], and that the allocation concealment methods should be reported in detail in a publication of an RCT's results; however, a 2005 study determined that most RCTs have unclear allocation concealment in their protocols, in their publications, or both.<ref name="Pildal-2005">{{Cite journal |vauthors=Pildal J, Chan AW, Hróbjartsson A, Forfang E, Altman DG, Gøtzsche PC | title = Comparison of descriptions of allocation concealment in trial protocols and the published reports: cohort study | journal = BMJ | volume = 330 | issue = 7499 | page = 1049 | year = 2005 | doi = 10.1136/bmj.38414.422650.8F | pmid = 15817527 | pmc = 557221 }}</ref> On the other hand, a 2008 study of 146 [[meta-analysis|meta-analyses]] concluded that the results of RCTs with inadequate or unclear allocation concealment tended to be biased toward beneficial effects only if the RCTs' outcomes were [[Subjectivity|subjective]] as opposed to [[Objectivity (philosophy)|objective]].<ref name="Wood-2008">{{Cite journal |vauthors=Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman DG, Gluud C, Martin RM, Wood AJ, Sterne JA | title = Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study | journal = BMJ | volume = 336 | issue = 7644 | pages = 601–5 | year = 2008 | doi = 10.1136/bmj.39465.451748.AD | pmid = 18316340 | pmc = 2267990 }}</ref>
Some standard methods of ensuring allocation concealment include sequentially numbered, opaque, sealed envelopes (SNOSE); sequentially numbered containers; pharmacy controlled randomization; and central randomization.<ref name="Schulz-2002"/> It is recommended that allocation concealment methods be included in an RCT's [[Clinical trial protocol|protocol]], and that the allocation concealment methods should be reported in detail in a publication of an RCT's results; however, a 2005 study determined that most RCTs have unclear allocation concealment in their protocols, in their publications, or both.<ref name="Pildal-2005">{{Cite journal |vauthors=Pildal J, Chan AW, Hróbjartsson A, Forfang E, Altman DG, Gøtzsche PC | title = Comparison of descriptions of allocation concealment in trial protocols and the published reports: cohort study | journal = BMJ | volume = 330 | issue = 7499 | page = 1049 | year = 2005 | doi = 10.1136/bmj.38414.422650.8F | pmid = 15817527 | pmc = 557221 }}</ref> On the other hand, a 2008 study of 146 [[meta-analysis|meta-analyses]] concluded that the results of RCTs with inadequate or unclear allocation concealment tended to be biased toward beneficial effects only if the RCTs' outcomes were [[Subjectivity|subjective]] as opposed to [[Objectivity (philosophy)|objective]].<ref name="Wood-2008">{{Cite journal |vauthors=Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman DG, Gluud C, Martin RM, Wood AJ, Sterne JA | title = Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study | journal = BMJ | volume = 336 | issue = 7644 | pages = 601–5 | year = 2008 | doi = 10.1136/bmj.39465.451748.AD | pmid = 18316340 | pmc = 2267990 }}</ref>
Some standard methods of ensuring allocation concealment include sequentially numbered, opaque, sealed envelopes (SNOSE); sequentially numbered containers; pharmacy controlled randomization; and central randomization. It is recommended that allocation concealment methods be included in an RCT's protocol, and that the allocation concealment methods should be reported in detail in a publication of an RCT's results; however, a 2005 study determined that most RCTs have unclear allocation concealment in their protocols, in their publications, or both. On the other hand, a 2008 study of 146 meta-analyses concluded that the results of RCTs with inadequate or unclear allocation concealment tended to be biased toward beneficial effects only if the RCTs' outcomes were subjective as opposed to objective.
The number of treatment units (subjects or groups of subjects) assigned to control and treatment groups, affects an RCT's reliability. If the effect of the treatment is small, the number of treatment units in either group may be insufficient for rejecting the null hypothesis in the respective statistical test. The failure to reject the null hypothesis would imply that the treatment shows no statistically significant effect on the treated in a given test. But as the sample size increases, the same RCT may be able to demonstrate a significant effect of the treatment, even if this effect is small.
分配给控制组和治疗组的治疗单位(受试者或受试者组)的数量影响 RCT 的可靠性。如果治疗的效果很小，任何一组的治疗单位的数量都可能不足以在各自的统计检验中拒绝无效假设。拒绝零假设的失败将意味着治疗在给定的测试中对治疗没有统计学意义上的显著影响。但是随着样本量的增加，相同的随机对照试验也许能够证明治疗的显著效果，即使这种效果很小。
== Blinding ==
== Blinding ==
== Analysis of data ==
== Analysis of data ==
The types of statistical methods used in RCTs depend on the characteristics of the data and include:
The types of statistical methods used in RCTs depend on the characteristics of the data and include:
* For time-to-event outcome data that may be [[Censoring (statistics)|censored]], [[survival analysis]] (e.g., [[Kaplan–Meier estimator]]s and [[Cox proportional hazards model]]s for time to [[coronary heart disease]] after receipt of [[Hormone replacement therapy (menopause)|hormone replacement therapy in menopause]]<ref name="Rossouw-2002">{{Cite journal | author = Rossouw JE, Anderson GL, [[Ross Prentice|Prentice RL]], LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators | title = Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial | journal = [[J Am Med Assoc]] | volume = 288 | issue = 3 | pages = 321–33 | year = 2002 | pmid = 12117397 | doi = 10.1001/jama.288.3.321 | s2cid = 20149703 | url = https://escholarship.org/content/qt3mr6f93p/qt3mr6f93p.pdf?t=prll4c | doi-access = free }}</ref>) is appropriate.
* For time-to-event outcome data that may be [[Censoring (statistics)|censored]], [[survival analysis]] (e.g., [[Kaplan–Meier estimator]]s and [[Cox proportional hazards model]]s for time to [[coronary heart disease]] after receipt of [[Hormone replacement therapy (menopause)|hormone replacement therapy in menopause]]<ref name="Rossouw-2002">{{Cite journal | author = Rossouw JE, Anderson GL, [[Ross Prentice|Prentice RL]], LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators | title = Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial | journal = [[J Am Med Assoc]] | volume = 288 | issue = 3 | pages = 321–33 | year = 2002 | pmid = 12117397 | doi = 10.1001/jama.288.3.321 | s2cid = 20149703 | url = https://escholarship.org/content/qt3mr6f93p/qt3mr6f93p.pdf?t=prll4c | doi-access = free }}</ref>) is appropriate.
Due to the recent emergence of RCTs in social science, the use of RCTs in social sciences is a contested issue. Some writers from a medical or health background have argued that existing research in a range of social science disciplines lacks rigour, and should be improved by greater use of randomized control trials.
由于最近在社会科学中出现了 rct，rct 在社会科学中的应用是一个有争议的问题。一些有医学或健康背景的作家认为，一系列社会科学学科的现有研究缺乏严谨性，应该通过更多地使用随机对照试验来改进。
Researchers in transport science argue that public spending on programmes such as school travel plans could not be justified unless their efficacy is demonstrated by randomized controlled trials. Graham-Rowe and colleagues reviewed 77 evaluations of transport interventions found in the literature, categorising them into 5 "quality levels". They concluded that most of the studies were of low quality and advocated the use of randomized controlled trials wherever possible in future transport research.
Researchers in transport science argue that public spending on programmes such as school travel plans could not be justified unless their efficacy is demonstrated by randomized controlled trials. Graham-Rowe and colleagues reviewed 77 evaluations of transport interventions found in the literature, categorising them into 5 "quality levels". They concluded that most of the studies were of low quality and advocated the use of randomized controlled trials wherever possible in future transport research.
Two studies published in ''[[The New England Journal of Medicine]]'' in 2000 found that [[Observational study|observational studies]] and RCTs overall produced similar results.<ref name="Benson-2000">{{Cite journal |vauthors=Benson K, Hartz AJ | title = A comparison of observational studies and randomized, controlled trials | journal = [[N Engl J Med]] | volume = 342 | issue = 25 | pages = 1878–86 | year = 2000 | pmid = 10861324 | doi = 10.1056/NEJM200006223422506 }}</ref><ref name="Concato-2000">{{Cite journal |vauthors=Concato J, Shah N, Horwitz RI | title = Randomized, controlled trials, observational studies, and the hierarchy of research designs | journal = [[N Engl J Med]] | volume = 342 | issue = 25 | pages = 1887–92 | year = 2000 | url = http://nejm.highwire.org/cgi/content/full/342/25/1887 | pmid = 10861325 | doi = 10.1056/NEJM200006223422507 | pmc = 1557642 }}</ref> The authors of the 2000 findings questioned the belief that "observational studies should not be used for defining evidence-based medical care" and that RCTs' results are "evidence of the highest grade."<ref name="Benson-2000"/><ref name="Concato-2000"/> However, a 2001 study published in ''[[Journal of the American Medical Association]]'' concluded that "discrepancies beyond chance do occur and differences in estimated magnitude of treatment effect are very common" between observational studies and RCTs.<ref name="Ioannidis-2001">{{Cite journal |vauthors=Ioannidis JP, Haidich AB, Pappa M, Pantazis N, Kokori SI, Tektonidou MG, Contopoulos-Ioannidis DG, Lau J | title = Comparison of evidence of treatment effects in randomized and nonrandomized studies | journal = [[J Am Med Assoc]] | volume = 286 | issue = 7 | pages = 821–30 | year = 2001 | pmid = 11497536 | doi = 10.1001/jama.286.7.821 | citeseerx = 10.1.1.590.2854 }}</ref>
Two studies published in ''[[The New England Journal of Medicine]]'' in 2000 found that [[Observational study|observational studies]] and RCTs overall produced similar results.<ref name="Benson-2000">{{Cite journal |vauthors=Benson K, Hartz AJ | title = A comparison of observational studies and randomized, controlled trials | journal = [[N Engl J Med]] | volume = 342 | issue = 25 | pages = 1878–86 | year = 2000 | pmid = 10861324 | doi = 10.1056/NEJM200006223422506 }}</ref><ref name="Concato-2000">{{Cite journal |vauthors=Concato J, Shah N, Horwitz RI | title = Randomized, controlled trials, observational studies, and the hierarchy of research designs | journal = [[N Engl J Med]] | volume = 342 | issue = 25 | pages = 1887–92 | year = 2000 | url = http://nejm.highwire.org/cgi/content/full/342/25/1887 | pmid = 10861325 | doi = 10.1056/NEJM200006223422507 | pmc = 1557642 }}</ref> The authors of the 2000 findings questioned the belief that "observational studies should not be used for defining evidence-based medical care" and that RCTs' results are "evidence of the highest grade."<ref name="Benson-2000"/><ref name="Concato-2000"/> However, a 2001 study published in ''[[Journal of the American Medical Association]]'' concluded that "discrepancies beyond chance do occur and differences in estimated magnitude of treatment effect are very common" between observational studies and RCTs.<ref name="Ioannidis-2001">{{Cite journal |vauthors=Ioannidis JP, Haidich AB, Pappa M, Pantazis N, Kokori SI, Tektonidou MG, Contopoulos-Ioannidis DG, Lau J | title = Comparison of evidence of treatment effects in randomized and nonrandomized studies | journal = [[J Am Med Assoc]] | volume = 286 | issue = 7 | pages = 821–30 | year = 2001 | pmid = 11497536 | doi = 10.1001/jama.286.7.821 | citeseerx = 10.1.1.590.2854 }}</ref>
Have a stable and predictable relationship to exogenous factors
与外部因素有稳定和可预测的关系
与外部因素有稳定和可预测的关系
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"/>
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|url=http://www.cochrane.org/news/blog/how-well-do-meta-analyses-disclose-conflicts-interests-underlying-research-studies |title=How Well Do Meta-Analyses Disclose Conflicts of Interests in Underlying Research Studies | The Cochrane Collaboration |publisher=Cochrane.org |access-date=2011-08-19}}</ref>
A 2011 study done to disclose possible conflicts of interests 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 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."[97]
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 | title = Scope and impact of financial conflicts of interest in biomedical research: a systematic review | journal = [[J Am Med Assoc]] | volume = 289 | issue = 4 | pages = 454–65 | year = 2003 | pmid = 12533125 | doi = 10.1001/jama.289.4.454 }}</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 | title = Association between industry funding and statistically significant pro-industry findings in medical and surgical randomized trials | journal = [[Can Med Assoc J]] | volume = 170 | issue = 4 | pages = 477–80 | year = 2004 | url = http://ecmaj.com/cgi/content/full/170/4/477 | pmid = 14970094 | pmc = 332713 }}</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 | title = Discontinuation and non-publication of surgical randomised controlled trials: observational study | journal = [[BMJ]] | volume = 349 | page = g6870| year = 2014 | pmid = 25491195 | pmc = 4260649 | doi=10.1136/bmj.g6870}}</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 |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=2270–4 |year=2006 |pmid=16705108 |doi=10.1001/jama.295.19.2270 |doi-access=free }}</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. 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." 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. One possible reason for the pro-industry results in industry-funded published RCTs is publication bias.
有些 rct 完全或部分由医疗保健行业(如制药行业)资助，而不是政府、非营利组织或其他来源。2003年发表的一份系统综述研究报告发现，1986年至2002年间，有4篇文章比较了行业赞助和非行业赞助的 rct，在所有的文章中，行业赞助和正面研究结果之间存在相关性。2004年发表在主要医学和外科杂志上的一项关于1999-2001年的 rct 的研究表明，工业资助的 rct“更有可能与具有统计学意义的有利于工业的发现相关联。”这些结果已经反映在手术试验中，虽然行业资金并不影响试验中止率，但是与完成试验的发表机率较低相关。支持产业的结果在产业资助的已发表的研究报告中出现的一个可能的原因是出版偏见。
Category:Clinical research
Category:Clinical research
类别: 流行病学研究项目
类别: 流行病学研究项目
Category:Evidence-based practices
Category:Evidence-based practices
类别: 实验设计
类别: 实验设计
Category:Causal inference
Category:Causal inference
分类: 实验
分类: 实验
Category:Research methods
Category:Research methods