更改

[[File:Flowchart of Phases of Parallel Randomized Trial - Modified from CONSORT 2010.png|thumb|upright=1.5|Flowchart of four phases (enrollment, allocation, intervention, follow-up, and data analysis) of a parallel randomized trial of two groups (in a controlled trial, one of the interventions serves as the control), modified from the CONSORT (Consolidated Standards of Reporting Trials) 2010 Statement<ref name="Schulz-2010">{{Cite journal | author = Schulz KF, Altman DG, ((Moher D; for the CONSORT Group)) | title = CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials | journal = [[Br Med J]] | volume = 340 | pages = c332 | year = 2010 | doi = 10.1136/bmj.c332 | pmid = 20332509 | pmc = 2844940 }}</ref>|链接=Special:FilePath/Flowchart_of_Phases_of_Parallel_Randomized_Trial_-_Modified_from_CONSORT_2010.png]]

[[File:Flowchart of Phases of Parallel Randomized Trial - Modified from CONSORT 2010.png|thumb|upright=1.5|Flowchart of four phases (enrollment, allocation, intervention, follow-up, and data analysis) of a parallel randomized trial of two groups (in a controlled trial, one of the interventions serves as the control), modified from the CONSORT (Consolidated Standards of Reporting Trials) 2010 Statement<ref name="Schulz-2010">{{Cite journal | author = Schulz KF, Altman DG, ((Moher D; for the CONSORT Group)) | title = CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials | journal = [[Br Med J]] | volume = 340 | pages = c332 | year = 2010 | doi = 10.1136/bmj.c332 | pmid = 20332509 | pmc = 2844940 }}</ref>|链接=Special:FilePath/Flowchart_of_Phases_of_Parallel_Randomized_Trial_-_Modified_from_CONSORT_2010.png]]

Flowchart of four phases (enrollment, allocation, intervention, follow-up, and data analysis) of a parallel randomized trial of two groups (in a controlled trial, one of the interventions serves as the control), modified from the CONSORT (Consolidated Standards of Reporting Trials) 2010 Statement.

[来源：图片] Flowchart of four phases (enrollment, allocation, intervention, follow-up, and data analysis) of a parallel randomized trial of two groups (in a controlled trial, one of the interventions serves as the control), modified from the CONSORT (Consolidated Standards of Reporting Trials) 2010 Statement.

据修改的2010年CONSORT (综合报告试验标准)要求，流程图包括：两组平行随机试验分为登记、分配、干预、随访和数据分析四个阶段，在对照试验中，需要其中一项干预作为对照处理措施。  

据修改的2010年CONSORT (综合报告试验标准)要求，流程图包括：两组平行随机试验分为登记、分配、干预、随访和数据分析四个阶段，在对照试验中，需要其中一项干预作为对照处理措施。  

一个良好盲法的 RCT 通常被认为是临床试验的黄金标准。盲法随机对照试验通常用于检测医疗干预措施的效果，并且还可能提供关于药物反应等不良反应的信息。随机对照试验可以提供令人信服的证据，证明研究治疗对人类健康产生了影响。

一个良好盲法的 RCT 通常被认为是临床试验的黄金标准。盲法随机对照试验通常用于检测医疗干预措施的效果，并且还可能提供关于药物反应等不良反应的信息。随机对照试验可以提供令人信服的证据，证明研究治疗对人类健康产生了影响。

2004年， 医学杂志编辑国际委员会(ICMJE)宣布，所有在2005年7月1日之后考虑在该委员会12种杂志上发表之前，必须对试验进行注册。尽管如此，试验登记可能仍然延迟或根本不会发生。

2004年， 医学杂志编辑国际委员会(ICMJE)宣布，所有在2005年7月1日之后考虑在该委员会12种杂志上发表之前，必须对试验进行注册。尽管如此，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.

Medical journals have been slow in adapting policies requiring mandatory clinical trial registration as a prerequisite for publication.

An RCT may be blinded, (also called "masked") by "procedures that prevent study participants, caregivers, or outcome assessors from knowing which intervention was received."  The 2010 CONSORT Statement specifies that authors and editors should not use the terms "single-blind", "double-blind", and "triple-blind"; instead, reports of blinded RCT should discuss "If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how." "open", or (if the intervention is a medication) "open-label". In 2008 a study concluded that the results of unblinded RCTs tended to be biased toward beneficial effects only if the RCTs' outcomes were subjective as opposed to objective; In pragmatic RCTs, although the participants and providers are often unblinded, it is "still desirable and often possible to blind the assessor or obtain an objective source of data for evaluation of outcomes.") and other methods can be used.

An RCT may be blinded, (also called "masked") by "procedures that prevent study participants, caregivers, or outcome assessors from knowing which intervention was received."  The 2010 CONSORT Statement specifies that authors and editors should not use the terms "single-blind", "double-blind", and "triple-blind"; instead, reports of blinded RCT should discuss "If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how." "open", or (if the intervention is a medication) "open-label". In 2008 a study concluded that the results of unblinded RCTs tended to be biased toward beneficial effects only if the RCTs' outcomes were subjective as opposed to objective; In pragmatic RCTs, although the participants and providers are often unblinded, it is "still desirable and often possible to blind the assessor or obtain an objective source of data for evaluation of outcomes.") and other methods can be used.

一项RCT的盲法是指阻止研究参与者、照顾者或结果评估者知道哪些干预措施，这一程序也称“蒙面”。2010年 CONSORT 声明明确指出，作者和编辑不应使用”单盲”、”双盲”和”三盲”等术语; 相反，关于盲法 RCT 的报告应讨论”如果完成了，干预分配后谁被“蒙面”了(例如，参与者、护理提供者、评估结果的人员)以及如何完成”“开放”，或者(如果干预是一种药物)“开放标签”。2008年的一项研究得出结论认为，只有当随机对照试验的结果是主观的而不是客观的时候，非盲法随机对照试验的结果往往偏向于有益的结果; 在实用的随机对照试验中，尽管参与者和提供者往往是非盲的，但是”仍然需要并且往往可能使评估者“蒙面”，以获得评估结果的客观数据来源”以及其他方法。

 

 

 

 

一项RCT的盲法是指阻止研究参与者、照顾者或结果评估者知道哪些干预措施，这一程序也称“蒙面”。2010年CONSORT 声明明确指出，作者和编辑不应使用”单盲”、”双盲”和”三盲”等术语；相反，关于盲法 RCT 的报告应讨论”如果完成了，干预分配后谁被“蒙面”了(例如，参与者、护理提供者、评估结果的人员)以及如何完成”“开放”，或者(如果干预是一种药物)“开放标签”。2008年的一项研究得出结论认为，只有当随机对照试验的结果是主观的而不是客观的时候，非盲法随机对照试验的结果往往偏向于有益的结果；在实用的随机对照试验中，尽管参与者和提供者往往是非盲的，但是”仍然需要并且往往可能使评估者“蒙面”，以获得评估结果的客观数据来源”以及其他方法。

 

There are two processes involved in randomizing patients to different interventions. First is choosing a ''randomization procedure'' to generate an unpredictable sequence of allocations; this may be a simple random assignment of patients to any of the groups at equal probabilities, may be "restricted", or may be "adaptive." A second and more practical issue is ''allocation concealment'', which refers to the stringent precautions taken to ensure that the group assignment of patients are not revealed prior to definitively allocating them to their respective groups. Non-random "systematic" methods of group assignment, such as alternating subjects between one group and the other, can cause "limitless contamination possibilities" and can cause a breach of allocation concealment.<ref name="Schulz-2002"/>

There are two processes involved in randomizing patients to different interventions. First is choosing a ''randomization procedure'' to generate an unpredictable sequence of allocations; this may be a simple random assignment of patients to any of the groups at equal probabilities, may be "restricted", or may be "adaptive." A second and more practical issue is ''allocation concealment'', which refers to the stringent precautions taken to ensure that the group assignment of patients are not revealed prior to definitively allocating them to their respective groups. Non-random "systematic" methods of group assignment, such as alternating subjects between one group and the other, can cause "limitless contamination possibilities" and can cause a breach of allocation concealment.<ref name="Schulz-2002"/>

 

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:

The treatment allocation is the desired proportion of patients in each treatment arm.

The treatment allocation is the desired proportion of patients in each treatment arm.

 

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>

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."

* '''Maximize [[statistical power]]''', especially in [[Subgroup analysis|subgroup analyses]].  Generally, equal group sizes maximize statistical power, however, unequal groups sizes may be more powerful for some analyses (e.g., multiple comparisons of placebo versus several doses using Dunnett's procedure<ref>{{cite web|last=Rosenberger|first=James|title=STAT 503 - Design of Experiments|url=https://onlinecourses.science.psu.edu/stat503/node/16|publisher=Pennsylvania State University|access-date=24 September 2012}}</ref> ), and are sometimes desired for non-analytic reasons (e.g., patients may be more motivated to enroll if there is a higher chance of getting the test treatment, or regulatory agencies may require a minimum number of patients exposed to treatment).<ref name="Avins-1998">{{cite journal|last=Avins|first=A L|title="Can unequal be more fair? Ethics, subject allocation, and randomized clinical trials".|journal=J Med Ethics|year=1998|volume=24|pages=401–408|doi=10.1136/jme.24.6.401|issue=6|pmc=479141|pmid=9873981}}</ref>

* '''Maximize [[statistical power]]''', especially in [[Subgroup analysis|subgroup analyses]].  Generally, equal group sizes maximize statistical power, however, unequal groups sizes may be more powerful for some analyses (e.g., multiple comparisons of placebo versus several doses using Dunnett's procedure<ref>{{cite web|last=Rosenberger|first=James|title=STAT 503 - Design of Experiments|url=https://onlinecourses.science.psu.edu/stat503/node/16|publisher=Pennsylvania State University|access-date=24 September 2012}}</ref> ), and are sometimes desired for non-analytic reasons (e.g., patients may be more motivated to enroll if there is a higher chance of getting the test treatment, or regulatory agencies may require a minimum number of patients exposed to treatment).<ref name="Avins-1998">{{cite journal|last=Avins|first=A L|title="Can unequal be more fair? Ethics, subject allocation, and randomized clinical trials".|journal=J Med Ethics|year=1998|volume=24|pages=401–408|doi=10.1136/jme.24.6.401|issue=6|pmc=479141|pmid=9873981}}</ref>

This is a commonly used and intuitive procedure, similar to "repeated fair coin-tossing."<ref name="SchulzGrimes2002"/> Also known as "complete" or "unrestricted" randomization, it is [[Robust statistics|robust]] against both selection and accidental biases. However, its main drawback is the possibility of imbalanced group sizes in small RCTs.  It is therefore recommended only for RCTs with over 200 subjects.<ref name="Lachin-1988b">{{Cite journal |vauthors=Lachin JM, Matts JP, Wei LJ | title = Randomization in clinical trials: conclusions and recommendations | journal = [[Controlled Clinical Trials]] | volume = 9 | issue = 4 | pages = 365–74 | year = 1988 | pmid = 3203526 |  doi = 10.1016/0197-2456(88)90049-9 | hdl = 2027.42/27041 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/27041/1/0000029.pdf | hdl-access = free }}</ref>

This is a commonly used and intuitive procedure, similar to "repeated fair coin-tossing."<ref name="SchulzGrimes2002"/> Also known as "complete" or "unrestricted" randomization, it is [[Robust statistics|robust]] against both selection and accidental biases. However, its main drawback is the possibility of imbalanced group sizes in small RCTs.  It is therefore recommended only for RCTs with over 200 subjects.<ref name="Lachin-1988b">{{Cite journal |vauthors=Lachin JM, Matts JP, Wei LJ | title = Randomization in clinical trials: conclusions and recommendations | journal = [[Controlled Clinical Trials]] | volume = 9 | issue = 4 | pages = 365–74 | year = 1988 | pmid = 3203526 |  doi = 10.1016/0197-2456(88)90049-9 | hdl = 2027.42/27041 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/27041/1/0000029.pdf | hdl-access = free }}</ref>

如果医学技术领域出现颠覆性创新，在RCT中，对照组的结果变得“明显”—－即对照组出现明显差的结局。这要么由于其他的前述测试，要么是在 RCT 本身的初始阶段， 那么在 RCT 中很难从伦理上检验这一点。从伦理上讲，过早地中止 RCT 可能是必要的，而在未来的 RCT 中，获得伦理批准(以及患者同意)以阻止控制组的创新可能是不可行的。

如果医学技术领域出现颠覆性创新，在RCT中，对照组的结果变得“明显”—－即对照组出现明显差的结局。这要么由于其他的前述测试，要么是在 RCT 本身的初始阶段， 那么在 RCT 中很难从伦理上检验这一点。从伦理上讲，过早地中止 RCT 可能是必要的，而在未来的 RCT 中，获得伦理批准(以及患者同意)以阻止控制组的创新可能是不可行的。

== 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: