在非随机对照研究质量评价——非随机干预性研究偏倚风险评估工具ROBINS-I (Risk of Bias in Non-randomized Studies-of Intervention) (一)一文中介绍了ROBINS-I的使用方法，本文主要介绍评估清单中的混杂偏倚、研究对象选择的偏倚、干预分类的偏倚、偏离既定干预措施的偏倚。缺失数据的偏倚、结局测量的偏倚、结果选择性报告的偏倚详见非随机对照研究质量评价——非随机干预性研究偏倚风险评估工具ROBINS-I (Risk of Bias in Non-randomized Studies-of Intervention) (三)。
关键词：非随机对照研究质量评价; 非随机干预性研究偏倚风险评估; NRSI; ROBINS-I
二、评估清单
| Table 3 | The Risk Of Bias In Non-randomized Studies——of Interventions (ROBINS-I) assessment tool | |||
| 表3 | 非随机研究的偏倚风险评估工具ROBINS-I | |||
| Bias domain 偏倚域 | Signalling questions信号问题 | Elaboration详细解释 | Response options回答选项 |
| Bias due to confounding 译文：混杂偏倚 | 1.1 Is there potential for confounding of the effect of intervention in this study? If N/PN to 1.1: the study can be considered to be at low risk of bias due to confounding and no further signalling questions need be considered If Y/PY to 1.1: determine whether there is a need to assess time-varying confounding | In rare situations, such as when studying harms that are very unlikely to be related to factors that influence treatment decisions, no confounding is expected and the study can be considered to be at low risk of bias due to confounding, equivalent to a fully randomized trial. There is no NI (No information) option for this signalling question. | Y/PY/PN/N |
| 译文：1.1 研究中是否可能存在影响干预效果的混杂因素？ 若1.1 回答否/可能否，可视为研究由于混杂因素导致偏倚的风险低，因此不需要额外的问题进行评估 若1.1回答是/可能是，需要进一步评价是否存在时间依赖性混杂 | 在极少数情况下，例如当研究不太可能与影响治疗决策的因素相关的伤害时，不会产生混杂，就算产生偏倚，也可以认为该研究偏倚风险较低，相当于完全随机试验。该问题没有NI (no information)选项 | 是/可能是/可能否/否 | |
| 1.2 Was the analysis based on splitting participants' follow up time according to intervention received? If N/PN: answer questions relating to baseline confounding (1.4 to 1.6) If Y/PY: go to question 1.3 | If participants could switch between intervention groups then associations between intervention and outcome may be biased by time-varying confounding. This occurs when prognostic factors influence switches between intended interventions. | NA/Y/PY/PN/N/NI | |
| 译文：1.2 是否根据受干预的不同对受试者的随访时间进行了分段，并以此时间分段进行分析? 若回答否/可能否，则回答与基线混杂有关的问题 (问题1.4-1.6) 若回答是/可能是，则回答向题1.3 | 译文：如果受试者可以在干预组之间进行切换，那么干预和结果之间的关联可能会因为混杂而产生偏倚。当预后因素影响干预之间的切换时，就会发生这种情况 | 不适用/是/可能是/可能否/否/未知 | |
| 1.3 Were intervention discontinuations or switches likely to be related to factors that are prognostic for the outcome? If N/PN: answer questions relating to baseline confounding (1.4 to 1.6) If Y/PY: answer questions relating to both baseline and time-varying confounding (1.7 and 1.8) | If intervention switches are unrelated to the outcome, for example when the outcome is an unexpected harm, then time-varying confounding will not be present and only control for baseline confounding is required. | NA/Y/PY/PN/N/NI | |
| 译文：1.3干预中断或变更是否可能与结局的预后因素相关？ 若回答为否/可能否，继续回答与基线混杂有关的问题 (问题 1.4-1.6) 若回答是/可能是，则继续回答与基线混杂和时间依赖性协变量引起的混杂均相关的问题(问题1.7-1.8) | 译文：如果干预变化与结果无关，如当结果是意外伤害时，则不会出现随时间变化的偏倚，只需要控制基线混杂即可 | 不适用/是/可能是/可能否/否/未知 | |
| Questions relating to baseline confounding only | |||
| 译文：仅与基线混杂有关的问题 | |||
| 1.4. Did the authors use an appropriate analysis method that controlled for all the important confounding domains? | Appropriate methods to control for measured confounders include stratification, regression, matching, standardization, and inverse probability weighting. They may control for individual variables or for the estimated propensity score. Inverse probability weighting is based on a function of the propensity score. Each method depends on the assumption that there is no unmeasured or residual confounding. | NA/Y/PY/PN/N/NI | |
| 译文：1.4 作者是否采用了恰当的分析方法控制所有重要的混杂？ | 译文：控制测量的混杂因素的合适方法包括分层、回归、匹配、标准化和逆概率加权。它们可以控制单个变量或估计的倾向性评分。逆概率加权是基于倾向性评分的函数。每种方法都基于没有未测量或残留混杂的假设 | 不适用/是/可能是/可能否/否/未知 | |
| 1.5. If Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study? | Appropriate control of confounding requires that the variables adjusted for are valid and reliable measures of the confounding domains. For some topics, a list of valid and reliable measures of confounding domains will be specified in the review protocol but for others such a list may not be available. Study authors may cite references to support the use of a particular measure. If authors control for confounding variables with no indication of their validity or reliability pay attention to the subjectivity of the measure. Subjective measures (e.g. based on self-report) may have lower validity and reliability than objective measures such as lab findings. | NA/Y/PY/PN/N/NI | |
| 译文：1.5 若问题 1.4 回答是/可能是，则回答研究中的变量是否可以真实可靠地测量了所需要控制的混杂 | 译文：对混杂的适当控制要求调整的变量是混杂域有效且可靠的度量。对于某些主题，将在审阅协议中指定混杂域的有效和可靠度量的列表，但对于其他主题，此类列表可能不可用。研究者可能会引用参考文献来支持为何使用特定措施。如果作者控制混杂变量而不表明其有效性或可靠性，则尤其要注意该措施的主观性。主观措施(如基于自我报告)可能比客观措施(如实验室检查结果)的有效性和可靠性更低 | 不适用/是/可能是/可能否/否/未知 | |
| 1.6. Did the authors control for any post-intervention variables that could have been affected by the intervention? | Controlling for post-intervention variables that are affected by intervention is not appropriate. Controlling for mediating variables estimates the direct effect of intervention and may introduce bias. Controlling for common effects of intervention and outcome introduces bias. | NA/Y/PY/PN/N/NI | |
| 译文：1.6 对于受干预影响的因素，作者是否控制了基线时间依赖性协变量引起的混杂 | 译文：控制受干预影响的干预后变量是不合适的。控制中介变量可估计干预的直接效果，并可能导致偏倚。控制干预措施和结果的共同作用会产生偏倚 | 不适用/是/可能是/可能否/否/未知 | |
| Questions relating to baseline and time-varying confounding | |||
| 译文：关于基线和时间依赖性混杂的问题 | |||
| 1.7. Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time-varying confounding? | Adjustment for time-varying confounding is necessary to estimate the effect of starting and adhering to intervention, in both randomized trials and NRSI. Appropriate methods include those based on inverse probability weighting.Standard regression models that include time-updated confounders may be problematic if time-varying confounding is present. | NA/Y/PY/PN/N/NI | |
| 译文：1.7 作者是否采用了恰当的分析方法以控制所有重要的混杂因素以及时间依赖性协变量引起的混杂? | 译文：在随机对照研究和 NRSI 中，必须调整随时间变化的混杂因素，以估计开始和持续干预的效果。适当的方法如，逆概率加权、标准回归模型 | 不适用/是/可能是/可能否/否/未知 | |
| 1.8. If Y/PY to 1.7: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study? | See 1.5 above. | NA/Y/PY/PN/N/NI | |
| 译文：1.8 若问题1.7回答是/可能是，则回答研究中的变量是否可以真实可靠地测量所需要控制的混杂? | 译文：见上面的1.5 | 不适用/是/可能是/可能否/否/未知 | |
| Optional: Risk of bias judgement | See Table 2 | Low / Moderate / Serious / Critical / NI | |
| 译文：可选项：混杂偏倚的方向 | 见表2 | 低/中/高/极高/未知 | |
| Bias in selection of participants into the study 译文：研究对象选择的偏倚 | 2.1. Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention? If N/PN to 2.1: go to 2.4 | This domain is concerned only with selection into the study based on participant characteristics observed after the start of intervention. Selection based on characteristics observed before the start of intervention can be addressed by controlling for imbalances between experimental intervention and comparator groups in baseline characteristics that are prognostic for the outcome (baseline confounding). | Y/PY/PN/N/NI |
| 译文：2.1研究对象的选择(纳人研究或分析)是否根据干预开始后观察到的个体特征进行？ 若回答否/可能否：继续回答问题2.4 | 译文：该领域仅涉及根据干预开始后观察到的参与者特征进行的研究对象选择。根据干预开始之前观察到的特征进行选择，可以通过控制干预组和对照组之间基线、预后不良的基线之间的不平衡来解决(基线偏倚) | 是/可能是/可能否/否/未知 | |
| 2.2. If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention? | Selection bias occurs when selection is related to an effect of either intervention or a cause of intervention and an effect of either the outcome or a cause of the outcome. Therefore, the result is at risk of selection bias if selection into the study is related to both the intervention and the outcome. | NA/Y/PY/PN/N/NI | |
| 2.2 若问题2.1回答是/可能是，则回答在干预开始后，是否有因素既影响研究对象的纳入，同时也与干预有关 | 不适用/是/可能是/可能否/否/未知 | ||
| 2.3. If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome? | NA/Y/PY/PN/N/NI | ||
| 译文：2.3 若问题 2.2回答是/可能是，则回答在干预开始后，是否有因素既影响研究对象的纳人，同时也受结局的发生或导致结局发生原因的影响 | 译文：当选择与干预或干预的原因以及结果或结果的原因相关时，就会发生选择偏倚。因此，如果选择进入研究既涉及干预又涉及结果，则存在选择偏倚的风险 | 不适用/是/可能是/可能否/否/未知 | |
| 2.4. Do start of follow-up and start of intervention coincide for most participants? | If participants are not followed from the start of the intervention then a period of follow up has been excluded, and individuals who experienced the outcome soon after intervention will be missing from analyses. This problem may occur when prevalent, rather than new (incident), users of the intervention are included in analyses. | Y/PY/PN/N/NI | |
| 译文：2.4 大多数受试者的随访与干预的起始时间是否一致？ | 译文：如果未从干预开始时随访受试者，则表明排除了一段时间的随访，如果干预后不久发生结局事件的受试者将无法进行分析。当干预中主要是现患病例而不是新发病例时则可能会出现此问题 | 是/可能是/可能否/否/未知 | |
| 2.5. If Y/PY to 2.2 and 2.3, or N/PN to2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases? | It is in principle possible to correct for selection biases, for example by using inverse probability weights to create a pseudo-population in which the selection bias has been removed, or by modelling the distributions of the missing participants or follow up times and outcome events and including them using missing data methodology. However such methods are rarely used and the answer to this question will usually be “No” | NA/Y/PY/PN/N/NI | |
| 译文：2.5 若问题 2.2 和 23 回答是/可能是，或者若问题 2.4 回答否/可能否，则回答所运用的校正方法是否能校正选择偏倚 | 译文：原则上可以校正选择偏倚，如：通过使用逆概率权重生成虚拟样本，则选择偏倚可被规避，或者通过对缺失受试者的分布或后续时间和结果事件进行建模。但是，此类方法很少使用，并且对该问题的答案通常为“否” | 不适用/是/可能是/可能否/否/未知 | |
| Optional: Risk of bias judgement | See Table 2 | Low / Moderate / Serious / Critical / NI | |
| 译文：可选项：研究对象选择偏倚的方向 | 见表2 | 低/中/高/极高/未知 | |
| Bias in classification of interventions 译文：干预分类的偏倚 | 3.1 Were intervention groups clearly defined? | A pre-requisite for an appropriate comparison of interventions is that the interventions are well defined. Ambiguity in the definition may lead to bias in the classification of participants. For individual-level interventions, criteria for considering individuals to have received each intervention should be clear and explicit, covering issues such as type, setting, dose, frequency,intensity and/or timing of intervention. For population-level interventions (e.g. measures to control air pollution), the question relates to whether the population is clearly defined, and the answer is likely to be 'Yes'. | Y/PY/PN/N/NI |
| 译文：3.1 是否对各个干预组进行了清晰地界定？ | 译文：科学比较干预措施的前提条件是对干预措施进行明确定义。定义上的歧义可能会导致受试者分类的偏倚。对于施加给个体的干预措施，要考虑个体接受每种干预措施的标准是否清楚明确，需要涵盖诸如干预措施的类型、设置、剂量、频率、强度和/或时机等问题。对于施加给群体的干预措施(如控制空气污染的措施)，重点在于对群体进行明确定义，答案很可能是“是” | 是/可能是/可能否/否/未知 | |
| 3.2 Was the information used to define intervention groups recorded at the start of the intervention? | In general, if information about interventions received is available from sources that could not have been affected by subsequent outcomes, then differential misclassification of intervention status is unlikely. Collection of the information at the time of the intervention makes it easier to avoid such misclassification. For population-level interventions (e.g. measures to control air pollution), the answer to this question is likely to be 'Yes' | Y/PY/PN/N/NI | |
| 译文：3.2是否在干预起始时就对各组干预信息进行了记录？ | 译文：一般而言，如果干预措施的信息来源不太可能受到后续结果的影响，那么干预状态进行错误分类的可能性就较小。在干预时收集信息更容易避免这种错误分类。对于群体干预措施(如控制空气污染的措施)，该问题的答案可能是“是” | 是/可能是/可能否/否/未知 | |
| 3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome? | Collection of the information at the time of the intervention may not be sufficient to avoid bias. The way in which the data are collected for the purposes of the NRSI should also avoid misclassification. | Y/PY/PN/N/NI | |
| 译文：3.3 干预组的划分是否会因为知晓结局或结局相关风险而受到影响? | 译文：干预时收集的信息可能不足以避免偏倚。出于 NRSI 的目的收集数据的方式也应避免分类错误 | 是/可能是/可能否/否/未知 | |
| Optional: Risk of bias judgement | See Table 2 | Low / Moderate / Serious / Critical / NI | |
| 译文：可选项：干预分类偏倚的方向 | 见表2 | 低/中/高/极高/未知 | |
| Bias due to deviations from intended interventions 译文：偏离既定干预措施的偏倚 | If your aim for this study is to assess the effect of assignment to intervention, answer questions 4.1 and 4.2 | ||
| 译文：如果您的研究目的是评价干预的分配效应，请继续回答问题 4.1和4.2 | |||
| 4.1. Were there deviations from the intended intervention beyond what would be expected in usual practice? | Deviations that happen in usual practice following the intervention (for example, cessation of a drug intervention because of acute toxicity) are part of the intended intervention and therefore do not lead to bias in the effect of assignment to intervention.Deviations may arise due to expectations of a difference between intervention and comparator (for example because participants feel unlucky to have been assigned to the comparator group and therefore seek the active intervention, or components of it, or other interventions). Such deviations are not part of usual practice, so may lead to biased effect estimates. However these are not expected in observational studies of individuals in routine care. | Y/PY/PN/N/NI | |
| 译文：4.1是否存在超出通常做法的偏离预期干预措施的情况？ | 译文：干预后在常规实践中发生的偏倚(如由于急性毒性而停止用药)是预期干预的一部分，因此不会导致偏倚。由于干预措施和对照措施之间存在差异而导致受试者行为差异，则会产生偏倚(如被分配到对照组的受试者会感到不幸运，并因此寻求积极的干预措施或其他干预措施)。这样的偏差不是常规做法的一部分，因此可能导致偏倚。但是，在常规医护人员的观察研究中，这些都难以预料 | 是/可能是/可能否/否/未知 | |
| 4.2. If Y/PY to 4.1: Were these deviations from intended intervention unbalanced between groups and likely to have affected the outcome? | Deviations from intended interventions that do not reflect usual practice will be important if they affect the outcome, but not otherwise. Furthermore,bias will arise only if there is imbalance in the deviations across the two groups. | NA/Y/PY/PN/N/NI | |
| 译文：4.2 若在 4.1中回答是/可能是，则回答：干预变化是否在组间不均衡，并可能对研究结局造成影响？ | 译文：非通常做法的偏离预期的干预措施，如果影响结果则很重要，否则便不重要。此外，只有当两组之间的偏差不均衡时，才会出现偏倚 | 不适用/是/可能是/可能否/否/未知 | |
| If your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.6 | |||
| 译文：如果研究目的是评价干预的依从效应，请继续回答问题4.3-4.6 | |||
| 4.3. Were important co-interventions balanced across intervention groups? | Risk of bias will be higher if unplanned co-interventions were implemented in a way that would bias the estimated effect of intervention. Co-interventions will be important if they affect the outcome, but not otherwise. Bias will arise only if there is imbalance in such co-interventions between the intervention groups. Consider the co-interventions, including any pre-specified co-interventions, that are likely to affect the outcome and to have been administered in this study. Consider whether these co-interventions are balanced between intervention groups. | Y/PY/PN/N/NI | |
| 译文：4.3 重要的伴随干预措施在组间是否均衡？ | 译文：如果计划外联合干预措施会使干预的效果产生偏差，则发生偏倚的风险将更高。如果这些措施会影响结果，则很重要，否则就不重要。仅当比较组之间的这种共同干预不均衡时，才会出现偏倚。需要考虑可能影响结局并在本研究中给予的联合干预措施，包括任何预先规定的联合干预措施；考虑这些共同干预措施在组间是否均衡 | 是/可能是/可能否/否/未知 | |
| 4.4. Was the intervention implemented successfully for most participants? | Risk of bias will be higher if the intervention was not implemented as intended by, for example, the health care professionals delivering care during the trial. Consider whether implementation of the intervention was successful for most participants. | Y/PY/PN/N/NI | |
| 译文：4.4 计划的干预措施在大多数受试者中是否可成功实施？ | 译文：如果干预措施未按预期实施，例如，在试验期间对较多的受试者未施加预计的干预措施，则偏倚风险将更高。需要考虑干预措施是否对大多数受试者都是成功实施的。 | 是/可能是/可能否/否/未知 | |
| 4.5. Did study participants adhere to the assigned intervention regimen? | Risk of bias will be higher if participants did not adhere to the intervention as intended. Lack of adherence includes imperfect compliance, cessation of intervention, crossovers to the comparator intervention and switches to another active intervention. Consider available information on the proportion of study participants who continued with their assigned intervention throughout follow up, and answer 'No' or 'Probably No' if this proportion is high enough to raise concerns. Answer 'Yes' for studies of interventions that are administered once, so that imperfect adherence is not possible.We distinguish between analyses where follow-up time after interventions switches (including cessation of intervention) is assigned to (1) the new intervention or (2) the original intervention. (1) is addressed under time-varying confounding, and should not be considered further here. | Y/PY/PN/N/NI | |
| 译文：4.5 研究对象是否依从了分配的干预措施？ | 译文：如果受试者没有按照预期坚持干预，则偏倚风险会更高。缺乏依从性包括不完全依从、停止干预、交叉到对照干预措施和改用另一种积极干预措施。需要考虑在整个随访期间接受非预期干预的受试者比例，如果该比例较高，则回答“否”或“可能否”。 对于一次给药的干预研究，回答“是”，因为不可能存在不完全依从。在分析时，我们应该区分干预转换(包括停止干预)后的随访时间是分配给新干预措施还是原始干预措施。前者是在时间依赖性混杂因素问题时需要解决的，这里不需要进一步考虑。 | 是/可能是/可能否/否/未知 | |
| 4.6. If N/PN to 4.3, 4.4 or 4.5: Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention? | It is possible to conduct an analysis that corrects for some types of deviation from the intended intervention. Examples of appropriate analysis strategies include inverse probability weighting or instrumental variable estimation. It is possible that a paper reports such an analysis without reporting information on the deviations from intended intervention, but it would be hard to judge such an analysis to be appropriate in the absence of such information. Specialist advice may be needed to assess studies that used these approaches.If everyone in one group received a co-intervention, adjustments cannot be made to overcome this. | NA/Y/PY/PN/N/NI | |
| 译文：4.6 如在4.3、4.4或4.5中回答否/可能否，则不回答是否采用了恰当的方法估计干预的依从效果 | 译文：可以通过分析纠正与预期干预措施相关的某些偏倚。合适的分析策略包括逆概率加权或工具变量。在论文中可能仅报告了采用的分析方法而没有报告偏离预期干预措施的信息，在缺少此类信息的情况下，很难判断这种分析是否合适，此时可能需要专家来评估如果一组中每个受试者都接受了共同干预，则无法通过调整来解决这种问题 | 不适用/是/可能是/可能否/否/未知 | |
| Optional: Risk of bias judgement | See Table 2 | Low / Moderate / Serious / Critical / NI | |
| 译文：可选项：偏离既定干预措施的偏倚方向 | 见表2 | 低/中/高/极高/未知 | |
注：本文内容是参考相关文献后对非随机干预性研究偏倚风险评估工具ROBINS-I (Risk of Bias in Non-randomized Studies-of Intervention)的概述，仅代表本网站观点。关于ROBINS-I 的更多内容详见网站(https://methods.cochrane.org/bias/risk-bias-non-randomized-studies-interventions)或论文ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions。
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