更改

== Reporting of results ==

== Reporting of results ==

Is applied in a context or setting similar to that which applies to the control group

<li value="5">The ''CONSORT 2010 Statement'' is "an evidence-based, minimum set of recommendations for reporting RCTs." The CONSORT 2010 checklist contains 25 items (many with sub-items) focusing on "individually randomised, two group, parallel trials" which are the most common type of RCT.

The ''[[Consolidated Standards of Reporting Trials|CONSORT 2010 Statement]]'' is "an evidence-based, minimum set of recommendations for reporting RCTs."<ref name="CONSORT">{{cite web |url=http://www.consort-statement.org |title=Welcome to the CONSORT statement Website |author=CONSORT Group |access-date=2010-03-29}}</ref> The CONSORT 2010 checklist contains 25 items (many with sub-items) focusing on "individually randomised, two group, parallel trials" which are the most common type of RCT.<ref name="Schulz-2010"/>

CONSORT 2010声明是“一套基于证据的报告随机对照试验的最低建议。”CONSORT 2010核对表包含25个项目(许多带有子项目)，重点关注“个体随机、两组、平行试验”，这是RCT最常见的类型。

对于其他RCT研究设计，“CONSORT扩展版”已经发布，一些例子是:

 

* CONSORT 2010 声明: 扩展至聚类随机试验

* CONSORT 2010 声明: 非药物治疗干预

 

 

 

 

 

For other RCT study designs, "[[Consolidated Standards of Reporting Trials|CONSORT extensions]]" have been published, some examples are:

 

* Consort 2010 Statement: Extension to Cluster Randomised Trials<ref name="CONSORT2010-EXTENSION-CLUSTER">{{Cite journal |vauthors=Campbell MK, Piaggio G, Elbourne DR, Altman DG| title = Consort 2010 statement: extension to cluster randomised trials | journal = [[BMJ]] | volume = 345| pages = e5661 | year = 2012  | pmid = 22951546 | doi = 10.1136/bmj.e5661 | doi-access = free }}</ref>

 

 

 

* Consort 2010 Statement: Non-Pharmacologic Treatment Interventions<ref name="CONSORT2010-EXTENSION-NON-PHARMACOLOGIC-1">{{Cite journal |vauthors=Boutron I, Moher D, Altman DG, Schulz K, Ravaud P| title = Extending the CONSORT Statement to randomized trials of nonpharmacologic treatment: explanation and elaboration | journal = [[Annals of Internal Medicine]] | volume = 148| issue = 4 | year = 2008 | pages=295–309  | pmid = 18283207 | doi=10.7326/0003-4819-148-4-200802190-00008| doi-access = free }}</ref><ref name="CONSORT2010-EXTENSION-NON-PHARMACOLOGIC-2">{{Cite journal |vauthors=Boutron I, Moher D, Altman DG, Schulz K, Ravaud P| title = Methods and Processes of the CONSORT Group: Example of an Extension for Trials Assessing Nonpharmacologic Treatments | journal = [[Annals of Internal Medicine]] | volume = 148| issue = 4 | year = 2008  | pmid = 18283201 | doi=10.7326/0003-4819-148-4-200802190-00008-w1 | pages=W60–6| doi-access = free }}</ref>

 

 

 

 

=== Relative importance and observational studies ===

=== Relative importance and observational studies ===

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, 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.

 

 

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 other lines of reasoning question RCTs' contribution to scientific knowledge beyond other types of studies:

Two other lines of reasoning question RCTs' contribution to scientific knowledge beyond other types of studies:

* If study designs are ranked by their potential for new discoveries, then [[Anecdotal evidence#Scientific context|anecdotal evidence]] would be at the top of the list, followed by observational studies, followed by RCTs.<ref name="Vandenbroucke-2008">{{Cite journal | author = Vandenbroucke JP | title = Observational research, randomised trials, and two views of medical science | journal = [[PLoS Med]] | volume = 5 | issue = 3 | pages = e67 | year = 2008 | doi = 10.1371/journal.pmed.0050067 | pmid = 18336067 | pmc = 2265762 }}</ref>

* If study designs are ranked by their potential for new discoveries, then anecdotal evidence would be at the top of the list, followed by observational studies, followed by RCTs.

* RCTs may be unnecessary for treatments that have dramatic and rapid effects relative to the expected stable or progressively worse natural course of the condition treated.<ref name="Black-1996"/><ref name="Glasziou-2007">{{Cite journal |vauthors=Glasziou P, Chalmers I, Rawlins M, McCulloch P | title = When are randomised trials unnecessary? Picking signal from noise | journal = [[Br Med J]] | volume = 334 | issue = 7589 | pages = 349–51 | year = 2007 | doi = 10.1136/bmj.39070.527986.68 | pmc=1800999 | pmid = 17303884 }}</ref> One example is [[History of cancer chemotherapy#Combination chemotherapy|combination chemotherapy]] including [[cisplatin]] for [[Metastasis|metastatic]] [[testicular cancer]], which increased the cure rate from 5% to 60% in a 1977 non-randomized study.<ref name="Glasziou-2007"/><ref name="Einhorn-2002">{{Cite journal | author = Einhorn LH | author-link = Lawrence Einhorn | title = Curing metastatic testicular cancer | journal = [[Proc Natl Acad Sci U S A]] | volume = 99 | issue = 7 | pages = 4592–5 | year = 2002 | doi = 10.1073/pnas.072067999 | pmid = 11904381 | pmc = 123692 }}</ref>

* RCTs may be unnecessary for treatments that have dramatic and rapid effects relative to the expected stable or progressively worse natural course of the condition treated. One example is combination chemotherapy including cisplatin for metastatic testicular cancer, which increased the cure rate from 5% to 60% in a 1977 non-randomized study.

 

 

 

 

=== Interpretation of statistical results ===

=== Interpretation of statistical results ===

Like all statistical methods, RCTs are subject to both [[type I and type II errors|type I ("false positive") and type II ("false negative") statistical errors]]. Regarding Type I errors, a typical RCT will use 0.05 (i.e., 1 in 20) as the probability that the RCT will falsely find two equally effective treatments significantly different.<ref name="Wittes-2002">{{Cite journal | author = Wittes J | title = Sample size calculations for randomized controlled trials | journal = [[Epidemiol Rev]] | volume = 24 | issue = 1 | pages = 39–53 | year = 2002 | doi = 10.1093/epirev/24.1.39 | pmid = 12119854 | doi-access = free }}</ref> Regarding Type II errors, despite the publication of a 1978 paper noting that the [[sample size]]s of many "negative" RCTs were too small to make definitive conclusions about the negative results,<ref name="Freiman-1978">{{Cite journal | doi = 10.1056/NEJM197809282991304 |vauthors=Freiman JA, Chalmers TC, ((Smith H Jr)), Kuebler RR | title = The importance of beta, the type II error and sample size in the design and interpretation of the randomized control trial. Survey of 71 "negative" trials | journal = [[N Engl J Med]] | volume = 299 | issue = 13 | pages = 690–4 | year = 1978 | pmid = 355881 }}</ref> by 2005-2006 a sizeable proportion of RCTs still had inaccurate or incompletely reported sample size calculations.<ref name="Charles-2009">{{Cite journal |vauthors=Charles P, Giraudeau B, Dechartres A, Baron G, Ravaud P | title = Reporting of sample size calculation in randomised controlled trials: review | journal = [[Br Med J]] | volume = 338 | pages = b1732 | date = 2009-05-12 | doi = 10.1136/bmj.b1732 | pmid = 19435763 | pmc = 2680945 }}</ref>

Like all statistical methods, RCTs are subject to both type I ("false positive") and type II ("false negative") statistical errors. Regarding Type I errors, a typical RCT will use 0.05 (i.e., 1 in 20) as the probability that the RCT will falsely find two equally effective treatments significantly different. Regarding Type II errors, despite the publication of a 1978 paper noting that the sample sizes of many "negative" RCTs were too small to make definitive conclusions about the negative results, by 2005-2006 a sizeable proportion of RCTs still had inaccurate or incompletely reported sample size calculations.

 

 

 

 

=== Peer review ===

=== Peer review ===

 

Peer review of results is an important part of the scientific method. Reviewers examine the study results for potential problems with design that could lead to unreliable results (for example by creating a systematic bias), evaluate the study in the context of related studies and other evidence, and evaluate whether the study can be reasonably considered to have proven its conclusions. To underscore the need for peer review and the danger of over-generalizing conclusions, two Boston-area medical researchers performed a randomized controlled trial in which they randomly assigned either a parachute or an empty backpack to 23 volunteers who jumped from either a biplane or a helicopter. The study was able to accurately report that parachutes fail to reduce injury compared to empty backpacks. The key context that limited the general applicability of this conclusion was that the aircraft were parked on the ground, and participants had only jumped about two feet.

 

 

 

[[Peer review]] of results is an important part of the [[scientific method]]. Reviewers examine the study results for potential problems with design that could lead to unreliable results (for example by creating a [[systematic bias]]), evaluate the study in the context of related studies and other evidence, and evaluate whether the study can be reasonably considered to have proven its conclusions. To underscore the need for peer review and the danger of over-generalizing conclusions, two Boston-area medical researchers performed a randomized controlled trial in which they randomly assigned either a parachute or an empty backpack to 23 volunteers who jumped from either a biplane or a helicopter. The study was able to accurately report that parachutes fail to reduce injury compared to empty backpacks. The key context that limited the general applicability of this conclusion was that the aircraft were parked on the ground, and participants had only jumped about two feet.<ref>{{cite news |url=https://www.npr.org/sections/health-shots/2018/12/22/679083038/researchers-show-parachutes-dont-work-but-there-s-a-catch |title=Researchers Show Parachutes Don't Work, But There's A Catch |date=22 Dec 2018 |author=Richard Harris}}</ref>

 

 

== Advantages ==

== Advantages ==

* 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 | author = Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ; GRADE Working Group | title = What is "quality of evidence" and why is it important to clinicians? | journal = BMJ | volume = 336 | issue = 7651 | pages = 995–8 |year = 2008 | doi = 10.1136/bmj.39490.551019.BE | pmc = 2364804 | pmid = 18456631 }}</ref>

* 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 | author = Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ; GRADE Working Group | title = What is "quality of evidence" and why is it important to clinicians? | journal = BMJ | volume = 336 | issue = 7651 | pages = 995–8 |year = 2008 | doi = 10.1136/bmj.39490.551019.BE | pmc = 2364804 | pmid = 18456631 }}</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 |url= http://www.cebm.net/index.aspx?o=1025 |title= Levels of evidence |author= Oxford Centre for Evidence-based Medicine |date=2011-09-16 |access-date=2012-02-15}}</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 |url= http://www.cebm.net/index.aspx?o=1025 |title= Levels of evidence |author= Oxford Centre for Evidence-based Medicine |date=2011-09-16 |access-date=2012-02-15}}</ref>

* 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, etal | 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 = 1701–12 | year = 2004 | 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 | title = Understanding the divergent data on postmenopausal hormone therapy | journal = N Engl J Med | volume = 348 | issue = 7 | pages = 645–50 | year = 2003 | doi = 10.1056/NEJMsb022365 | pmid = 12584376 }}</ref><ref name="Vandenbroucke-2009">{{Cite journal | author = Vandenbroucke JP | title = The HRT controversy: observational studies and RCTs fall in line | journal = Lancet | volume = 373 | issue = 9671 | pages = 1233–5 | year = 2009 | 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 | title = Changes in postmenopausal hormone replacement therapy use among women with high cardiovascular risk | journal = Am J Public Health | volume = 99 | issue = 12 | pages = 2184–7 | year = 2009 | doi = 10.2105/AJPH.2009.159889 | url = http://ajph.aphapublications.org/cgi/content/full/99/12/2184 | pmid = 19833984 | pmc=2775780}}</ref>

* 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, etal | 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 = 1701–12 | year = 2004 | 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 | title = Understanding the divergent data on postmenopausal hormone therapy | journal = N Engl J Med | volume = 348 | issue = 7 | pages = 645–50 | year = 2003 | doi = 10.1056/NEJMsb022365 | pmid = 12584376 }}</ref><ref name="Vandenbroucke-2009">{{Cite journal | author = Vandenbroucke JP | title = The HRT controversy: observational studies and RCTs fall in line | journal = Lancet | volume = 373 | issue = 9671 | pages = 1233–5 | year = 2009 | 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 | title = Changes in postmenopausal hormone replacement therapy use among women with high cardiovascular risk | journal = Am J Public Health | volume = 99 | issue = 12 | pages = 2184–7 | year = 2009 | doi = 10.2105/AJPH.2009.159889 | url = http://ajph.aphapublications.org/cgi/content/full/99/12/2184 | pmid = 19833984 | pmc=2775780}}</ref>

Many papers discuss the disadvantages of RCTs.<ref name="Black-1996">{{Cite journal | author = Black N | title = Why we need observational studies to evaluate the effectiveness of health care | journal = BMJ | volume = 312 | issue = 7040 | pages = 1215–8 | year = 1996 | pmid = 8634569 | pmc = 2350940 | doi=10.1136/bmj.312.7040.1215}}</ref><ref name="Bell & Peck-2012">{{Cite journal | author = Bell, S.H., & Peck, L.R. | title = Obstacles to and limitations of social experiments: 15 false alarms | journal = Abt Thought Leadership Paper Series | year = 2012 | url = http://abtassociates.com/white-papers/2012/obstacles-to-and-limitations-of-social-experiments.aspx }}</ref><ref name="Sanson-Fisher-2007">{{Cite journal |vauthors=Sanson-Fisher RW, Bonevski B, Green LW, D'Este C | title = Limitations of the randomized controlled trial in evaluating population-based health interventions | journal = Am J Prev Med | volume = 33 | issue = 2 | pages = 155–61 | year = 2007 | doi = 10.1016/j.amepre.2007.04.007 | url = http://www.ajpm-online.net/article/S0749-3797%2807%2900225-5/abstract | pmid = 17673104 }}</ref>  Among the most frequently cited drawbacks are:

Many papers discuss the disadvantages of RCTs.<ref name="Black-1996">{{Cite journal | author = Black N | title = Why we need observational studies to evaluate the effectiveness of health care | journal = BMJ | volume = 312 | issue = 7040 | pages = 1215–8 | year = 1996 | pmid = 8634569 | pmc = 2350940 | doi=10.1136/bmj.312.7040.1215}}</ref><ref name="Bell & Peck-2012">{{Cite journal | author = Bell, S.H., & Peck, L.R. | title = Obstacles to and limitations of social experiments: 15 false alarms | journal = Abt Thought Leadership Paper Series | year = 2012 | url = http://abtassociates.com/white-papers/2012/obstacles-to-and-limitations-of-social-experiments.aspx }}</ref><ref name="Sanson-Fisher-2007">{{Cite journal |vauthors=Sanson-Fisher RW, Bonevski B, Green LW, D'Este C | title = Limitations of the randomized controlled trial in evaluating population-based health interventions | journal = Am J Prev Med | volume = 33 | issue = 2 | pages = 155–61 | year = 2007 | doi = 10.1016/j.amepre.2007.04.007 | url = http://www.ajpm-online.net/article/S0749-3797%2807%2900225-5/abstract | pmid = 17673104 }}</ref>  Among the most frequently cited drawbacks are:

=== Time and costs ===

=== 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 | title = Effect of a US National Institutes of Health programme of clinical trials on public health and costs | journal = [[The Lancet|Lancet]] | volume = 367 | issue = 9519 | pages = 1319–27 | year = 2006 | doi = 10.1016/S0140-6736(06)68578-4 | url = http://www.chrp.org/pdf/HSR20070511.pdf | 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"/>

RCTs can be expensive; one study found 28 Phase III RCTs funded by the National Institute of Neurological Disorders and Stroke prior to 2000 with a total cost of US$335 million, 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.

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 |title=Case report on trial: Do you, Doctor, swear to tell the truth, the whole truth and nothing but the truth? |journal=J Med Case Rep |volume=5 |issue=1 |page=179 |date=May 2011 |pmid=21569508 |url=http://www.jmedicalcasereports.com/content/pdf/1752-1947-5-179.pdf|doi=10.1186/1752-1947-5-179 |pmc=3113995}}</ref>

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.

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"/>

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."

 

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。

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"/>

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.

=== Conflict of interest dangers ===

=== Transport science ===

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 &#124; The Cochrane Collaboration |publisher=Cochrane.org |access-date=2011-08-19}}</ref>

Dr. Steve Melia took issue with these conclusions, arguing that claims about the advantages of RCTs, in establishing causality and avoiding bias, have been exaggerated. He proposed the following eight criteria for the use of RCTs in contexts where interventions must change human behaviour to be effective:

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]

The intervention:

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>

# Are either known to the researchers, or else all possible alternatives can be tested

# Do not involve significant feedback mechanisms between the intervention group and external environments

# Have a stable and predictable relationship to exogenous factors

# Would act in the same way if the control group and intervention group were reversed

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.

RCTs have been used in evaluating a number of educational interventions. Between 1980 and 2016, over 1,000 reports of RCTs have been published. For example, a 2009 study randomized 260 elementary school teachers' classrooms to receive or not receive a program of behavioral screening, classroom intervention, and parent training, and then measured the behavioral and academic performance of their students. Another 2009 study randomized classrooms for 678 first-grade children to receive a classroom-centered intervention, a parent-centered intervention, or no intervention, and then followed their academic outcomes through age 19.

类别: 临床研究

类别: 临床研究

Category:Epidemiological study projects

Category:Epidemiological study projects

类别: 循证做法

类别: 循证做法

Category:Design of experiments

Category:Design of experiments

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