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第228行： − + − − 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. − − 同行评议是科学方法的重要组成部分。审查人员检查研究结果是否存在设计方面的潜在问题，这些问题可能导致不可靠的结果(例如产生系统性偏差) ，在相关研究和其他证据的背景下评估研究，并评估是否可以合理地认为该研究已经证明了其结论。为了强调同行评议的必要性和过于笼统结论的危险性，波士顿地区的两名医学研究人员进行了一次随机对照试验测试，他们随机给23名从双翼飞机或直升机上跳下的志愿者分配一个降落伞或一个空背包。这项研究能够准确地报告，与空背包相比，降落伞无法减少伤害。限制这一结论普遍适用性的关键背景是飞机停在地面上，参与者只跳了大约两英尺。 第238行：
第238行： + + − RCTs are considered to be the most reliable form of scientific evidence in the hierarchy of evidence that influences healthcare policy and practice because RCTs reduce spurious causality and bias. Results of RCTs may be combined in systematic reviews which are increasingly being used in the conduct of evidence-based practice. Some examples of scientific organizations' considering RCTs or systematic reviews of RCTs to be the highest-quality evidence available are:+ − − 在影响医疗政策和实践的证据层次中，随机对照试验被认为是最可靠的科学证据形式，因为它减少了虚假的因果关系和偏差。随机对照试验的结果可以结合进行系统评价，这种评价正越来越多地用于循证实践的操作。一些科学组织认为区域研究报告或对区域研究报告的系统审查是现有的最高质量证据的例子如下: − 第252行：
第251行： + + − Notable RCTs with unexpected results that contributed to changes in clinical practice include:+ − − 值得注意的随机对照试验，其意想不到的结果促成了临床实践的改变，包括: − 第264行：
第262行： − "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.+ − − − − Many papers discuss the disadvantages of RCTs. Among the most frequently cited drawbacks are: − − 许多论文讨论了 rct 的缺点。最常被提到的缺点是: − − 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> − + − RCTs can be expensive; 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.+ − − 随机对照试验可能很昂贵，每次随机对照试验的平均成本为1200万美元。然而，随机对照试验的投资回报率可能很高，因为同一项研究预测，28个 随机对照试验 产生的“10年社会净效益”是试验项目成本的46倍，其基础是评估一个质量调整寿命年等于当前人均国内生产总值的平均值。 − − − − − − It is costly to maintain RCTs for the years or decades that would be ideal for evaluating some interventions. − − 有些随机对照试验需要持续几年或几十年，花费巨大，但这些试验对于评价某些干预措施是理想的。 − − − − 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. − + 第301行：
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→Adaptive
有两个过程涉及到随机化的病人接受到不同的干预。首先是选择一个随机化程序来生成一个不可预测的分配序列；这可能是以相等的概率将患者随机分配到任何一组，可能是“受限的”，也可能是“适应性的”。第二个也是更实际的问题是隐藏分配，这是指在将患者明确分配到各自的组之前，采取严格的预防措施，以确保患者的组分配不被披露。非随机的“系统”组分配方法，如在一个组和另一个组之间交替患者，可能会造成“无限的污染可能性”，并可能导致分配隐藏的破坏。
有两个过程涉及到随机化的病人接受到不同的干预。首先是选择一个随机化程序来生成一个不可预测的分配序列；这可能是以相等的概率将患者随机分配到任何一组，可能是“受限的”，也可能是“适应性的”。第二个也是更实际的问题是隐藏分配，这是指在将患者明确分配到各自的组之前，采取严格的预防措施，以确保患者的组分配不被披露。非随机的“系统”组分配方法，如在一个组和另一个组之间交替患者，可能会造成“无限的污染可能性”，并可能导致分配隐藏的破坏。
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>
* '''Minimize allocation bias''' (or '''confounding'''). This may occur when [[covariate]]s that affect the outcome are not equally distributed between treatment groups, and the treatment effect is confounded with the effect of the covariates (i.e., an "accidental bias"<ref name="SchulzGrimes2002"/><ref name="Buyse-1989">{{Cite journal | author = Buyse ME | title = Analysis of clinical trial outcomes: some comments on subgroup analyses | journal = [[Controlled Clinical Trials]] | volume = 10 | issue = 4 Suppl | pages = 187S–194S | year = 1989 | pmid = 2605967 | doi = 10.1016/0197-2456(89)90057-3 }}</ref>). If the randomization procedure causes an imbalance in covariates related to the outcome across groups, estimates of effect may be [[bias of an estimator|biased]] if not adjusted for the covariates (which may be unmeasured and therefore impossible to adjust for).
* '''Minimize allocation bias''' (or '''confounding'''). This may occur when [[covariate]]s that affect the outcome are not equally distributed between treatment groups, and the treatment effect is confounded with the effect of the covariates (i.e., an "accidental bias"<ref name="SchulzGrimes2002"/><ref name="Buyse-1989">{{Cite journal | author = Buyse ME | title = Analysis of clinical trial outcomes: some comments on subgroup analyses | journal = [[Controlled Clinical Trials]] | volume = 10 | issue = 4 Suppl | pages = 187S–194S | year = 1989 | pmid = 2605967 | doi = 10.1016/0197-2456(89)90057-3 }}</ref>). If the randomization procedure causes an imbalance in covariates related to the outcome across groups, estimates of effect may be [[bias of an estimator|biased]] if not adjusted for the covariates (which may be unmeasured and therefore impossible to adjust for).
* '''最大化统计能力'''，尤其是在亚组分析中。一般来说，相等的组规模将最大化统计能力，然而，不相等的组规模对于某些分析来说可能更强大(例如，使用Dunnett程序对安慰剂与几个剂量进行多次比较)，并且有时由于非分析性原因而被采用(例如，如果有更高的机会获得试验治疗，患者可能更有动力登记，或者监管机构可能要求最少数量的患者接受治疗)。
* '''最小化选择偏差'''。如果调查人员可以有意识或无意识地在治疗之间优先招募患者，就可能发生这种情况。一个好的随机化过程是不可预测的，因此研究人员不能根据先前的治疗分配来猜测下一个受试者的分组。当已知以前的治疗方案时(如在非盲法研究中)或可以猜到(如果一种药物有明显的副作用)，选择偏倚的风险最高。
* '''最小化分配偏差(或混淆)'''。当影响结果的协变量在治疗组之间分布不均，并且治疗效果与协变量的效果混淆时(即“偶然偏差”)，可能会出现这种情况。如果随机化程序导致与各组结果相关的协变量失衡，如果不对协变量进行调整，效果估计可能会有偏差(这可能无法测量，因此无法调整)。
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.
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>
This is a commonly used and intuitive procedure, similar to "repeated fair coin-tossing." Also known as "complete" or "unrestricted" randomization, it is 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.这是一个常用且直观的程序，类似于“反复公平抛硬币”，也被称为“完全”或“无限制”随机化，它对选择和意外偏差都是稳健的。然而，它的主要缺点是在小的随机对照试验中群体规模不平衡的可能性。因此，建议仅用于受试者超过200人时进行随机对照试验。
==== Restricted ====
==== Restricted ====
To balance group sizes in smaller RCTs, some form of [[restricted randomization|"restricted" randomization]] is recommended.<ref name="Lachin-1988b"/> The major types of restricted randomization used in RCTs are:
To balance group sizes in smaller RCTs, some form of [[restricted randomization|"restricted" randomization]] is recommended.<ref name="Lachin-1988b"/> The major types of restricted randomization used in RCTs are:
* '''[[Randomized block design|Permuted-block randomization]]''' or '''blocked randomization''': a "block size" and "allocation ratio" (number of subjects in one group versus the other group) are specified, and subjects are allocated randomly within each block.<ref name="Schulz-2002"/> For example, a block size of 6 and an allocation ratio of 2:1 would lead to random assignment of 4 subjects to one group and 2 to the other. This type of randomization can be combined with "[[stratified randomization]]", for example by center in a [[multicenter trial]], to "ensure good balance of participant characteristics in each group."<ref name="Moher-2010"/> A special case of permuted-block randomization is ''random allocation'', in which the entire sample is treated as one block.<ref name="Schulz-2002"/> The major disadvantage of permuted-block randomization is that even if the block sizes are large and randomly varied, the procedure can lead to selection bias.<ref name="Lachin-1988a"/> Another disadvantage is that "proper" analysis of data from permuted-block-randomized RCTs requires stratification by blocks.<ref name="Lachin-1988b"/>
* '''[[Randomized block design|Permuted-block randomization]]''' or '''blocked randomization''': a "block size" and "allocation ratio" (number of subjects in one group versus the other group) are specified, and subjects are allocated randomly within each block.<ref name="Schulz-2002"/> For example, a block size of 6 and an allocation ratio of 2:1 would lead to random assignment of 4 subjects to one group and 2 to the other. This type of randomization can be combined with "[[stratified randomization]]", for example by center in a [[multicenter trial]], to "ensure good balance of participant characteristics in each group."<ref name="Moher-2010"/> A special case of permuted-block randomization is ''random allocation'', in which the entire sample is treated as one block.<ref name="Schulz-2002"/> The major disadvantage of permuted-block randomization is that even if the block sizes are large and randomly varied, the procedure can lead to selection bias.<ref name="Lachin-1988a"/> Another disadvantage is that "proper" analysis of data from permuted-block-randomized RCTs requires stratification by blocks.<ref name="Lachin-1988b"/>
* '''Adaptive biased-coin randomization''' methods (of which '''urn randomization''' is the most widely known type): In these relatively uncommon methods, the probability of being assigned to a group decreases if the group is overrepresented and increases if the group is underrepresented.<ref name="Schulz-2002"/> The methods are thought to be less affected by selection bias than permuted-block randomization.<ref name="Lachin-1988b"/>
* '''Adaptive biased-coin randomization''' methods (of which '''urn randomization''' is the most widely known type): In these relatively uncommon methods, the probability of being assigned to a group decreases if the group is overrepresented and increases if the group is underrepresented.<ref name="Schulz-2002"/> The methods are thought to be less affected by selection bias than permuted-block randomization.<ref name="Lachin-1988b"/>
为了平衡较小随机对照试验中的组规模，建议采用某种形式的“限制性”随机化。随机对照试验中主要使用的限制随机化类型有:
* '''置换区组随机化'''或'''区组随机化'''：规定了“区组大小”和“分配比例”(一组受试者相对于另一组受试者的数量)，受试者在每个区组内随机分配。例如，块大小为6，分配比例为2:1，将导致4个受试者随机分配到一个组，2个分配到另一个组。这种类型的随机化可以与“分层随机化”相结合，例如通过多中心试验中的中心，以“确保每个组中参与者特征的良好平衡。”置换块随机化的一个特殊情况是随机分配，其中整个样本被视为一个块。置换块随机化的主要缺点是，即使块大小很大且随机变化，该过程也会导致选择偏差。另一个缺点是，对置换区组随机对照试验数据的“适当”分析需要按区组分层。
* '''自适应有偏-硬币随机化方法'''（其中瓮随机化是最广为人知的类型）：在这些相对不常见的方法中，如果一个组的代表人数过多，被分配到该组的概率会降低，如果该组的代表人数不足，被分配到该组的概率会增加。这些方法被认为比置换块随机化受选择偏差的影响更小。
==== Adaptive ====
==== Adaptive ====
* '''Response-adaptive randomization''', also known as '''outcome-adaptive randomization''': The probability of being assigned to a group increases if the responses of the prior patients in the group were favorable.<ref name="Lachin-1988b"/> Although arguments have been made that this approach is more ethical than other types of randomization when the probability that a treatment is effective or ineffective increases during the course of an RCT, ethicists have not yet studied the approach in detail.<ref name="Rosenberger-1993">{{Cite journal |vauthors=Rosenberger WF, Lachin JM | title = The use of response-adaptive designs in clinical trials | journal = [[Controlled Clinical Trials]] | volume = 14 | issue = 6 | pages = 471–84 | year = 1993 | pmid = 8119063 | doi = 10.1016/0197-2456(93)90028-C }}</ref>
* '''Response-adaptive randomization''', also known as '''outcome-adaptive randomization''': The probability of being assigned to a group increases if the responses of the prior patients in the group were favorable.<ref name="Lachin-1988b"/> Although arguments have been made that this approach is more ethical than other types of randomization when the probability that a treatment is effective or ineffective increases during the course of an RCT, ethicists have not yet studied the approach in detail.<ref name="Rosenberger-1993">{{Cite journal |vauthors=Rosenberger WF, Lachin JM | title = The use of response-adaptive designs in clinical trials | journal = [[Controlled Clinical Trials]] | volume = 14 | issue = 6 | pages = 471–84 | year = 1993 | pmid = 8119063 | doi = 10.1016/0197-2456(93)90028-C }}</ref>
在随机对照试验中，至少使用了两种类型的“适应性”随机化程序，但频率远低于简单或限制性随机化：
* '''协变量自适应随机化'''，其中一种类型是最小化：被分配到一个组的概率是变化的，以便最小化“协变量不平衡”。据报道，最小化有“支持者和诋毁者”，因为只有第一个受试者的群组分配是真正随机选择的，该方法不一定能消除对未知因素的偏见。
* '''应答自适应随机化'''，也称为'''结果自适应随机化：'''如果组中先前患者的应答是有利的，则被分配到一个组的概率增加。虽然有人认为，当治疗有效或无效的概率在RCT过程中增加时，这种方法比其他类型的随机化更符合伦理，但伦理学家尚未详细研究这种方法。
=== Allocation concealment ===
=== Allocation concealment ===
"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.
“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群组分配，以便指定下一个病人的分配的故事比比皆是。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。一旦研究开始并在研究结束后，充分的分配隐藏应该会阻止患者和研究者发现治疗分配。与治疗相关的副作用或不良事件可能足够具体，足以向研究者或患者揭示分配情况，从而引入偏差或影响研究者收集的或受试者要求的任何主观参数。
“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。
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.
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.
一些确保分配隐藏的标准方法包括顺序编号、不透明、密封信封(SNOSE)；顺序编号的容器；药学控制的随机化；和中心随机化。分配隐藏方法被建议纳入RCT议定书，并在RCT结果的出版物中详细报告分配隐藏方法；然而，2005年的一项研究发现，大多数随机对照试验在其方案、出版物或两者中都有不清楚的分配隐藏。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。
=== Sample size ===
=== Sample size ===
{{Main|Sample size determination}}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.
{{Main|Sample size determination}}
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 hypothesis testing|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.<ref name="Glennerster-2013">{{Cite book | publisher = Princeton University Press | isbn = 9780691159249 | last = Glennerster | first = Rachel |author2=Kudzai Takavarasha | title = Running randomized evaluations: a practical guide | location = Princeton | date = 2013 |url=https://www.jstor.org/stable/j.ctt4cgd52 |chapter="Chapter 6" }}</ref>
分配给控制组和治疗组的治疗单位(受试者或受试者组)的样本量影响 RCT 的可靠性。如果治疗的效果很小，任何一组的治疗单位的样本量都可能不足以在各自的统计检验中拒绝无效假设（零假设）。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。
分配给控制组和治疗组的治疗单位(受试者或受试者组)的样本量影响 RCT 的可靠性。如果治疗的效果很小，任何一组的治疗单位的样本量都可能不足以在各自的统计检验中拒绝零假设。拒绝无效假设的失败意味着在给定的试验中，治疗对被治疗者没有统计学上的显著影响。但是随着样本量的增加，同样的RCT可能能够证明治疗的显著效果，即使这种效果很小。
== Blinding ==
== Blinding ==
{{main|Blinded experiment}}
{{main|Blinded experiment}}
An RCT may be [[Blind experiment|blinded]], (also called "masked") by "procedures that prevent study participants, caregivers, or outcome assessors from knowing which intervention was received."<ref name="Wood-2008"/> Unlike allocation concealment, blinding is sometimes inappropriate or impossible to perform in an RCT; for example, if an RCT involves a treatment in which active participation of the patient is necessary (e.g., [[physical therapy]]), participants cannot be blinded to the intervention.
An RCT may be [[Blind experiment|blinded]], (also called "masked") by "procedures that prevent study participants, caregivers, or outcome assessors from knowing which intervention was received."<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> Unlike allocation concealment, blinding is sometimes inappropriate or impossible to perform in an RCT; for example, if an RCT involves a treatment in which active participation of the patient is necessary (e.g., [[physical therapy]]), participants cannot be blinded to the intervention.
If a disruptive innovation in medical technology is developed, it may be difficult to test this ethically in an RCT if it becomes "obvious" that the control subjects have poorer outcomes—either due to other foregoing testing, or within the initial phase of the RCT itself. Ethically it may be necessary to abort the RCT prematurely, and getting ethics approval (and patient agreement) to withhold the innovation from the control group in future RCT's may not be feasible.
If a disruptive innovation in medical technology is developed, it may be difficult to test this ethically in an RCT if it becomes "obvious" that the control subjects have poorer outcomes—either due to other foregoing testing, or within the initial phase of the RCT itself. Ethically it may be necessary to abort the RCT prematurely, and getting ethics approval (and patient agreement) to withhold the innovation from the control group in future RCT's may not be feasible.